Publications

control of lymphocytic choriomeningitis virus infection in granzyme b deficient mice.	we have investigated whether granzyme b (gzmb) is required for effective cytotoxic t lymphocyte (ctl) mediated control of lymphocytic choriomeningitis virus (lcmv) infection. clearance of lcmv from tissues of gzmb-deficient (gzmb-) mice following intraperitoneal infection with lcmv was impaired compared with control mice; however, the virus was ultimately eliminated. the impaired clearance of lcmv in gzmb- mice was not due to a deficiency in the generation of lcmv-specific t cells. in addition, ...	2003	12504535
characterization of the genomic promoter of the prototypic arenavirus lymphocytic choriomeningitis virus.	the genome of the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) consists of two negative-sense, single-strand rna segments designated l and s. arenavirus genomes exhibit high sequence conservation at their 3' ends. all arenavirus genomes examined to date have a conserved terminal sequence element (3'-terminal 20 nucleotides [nt]) thought to be a highly conserved viral promoter. terminal complementarity between the 5' and 3' ends of the l and s rnas predicts the formation of a t ...	2003	12502835
cd4-independent protective cytotoxic t cells induced in early life by a non-replicative delivery system based on virus-like particles.	the relative immaturity of the neonatal immune system limits cd4(+) th1 and cytotoxic t lymphocyte (ctl) responses, and represents a significant challenge for the development of vaccines against intracellular pathogens. in this report, we demonstrate the ability of a non-replicative delivery system based on parvovirus-like particles (vlp) to induce ctl responses in the neonatal period. a single immunization of 1-week-old balb/c mice with recombinant vlp carrying a cd8(+) t cell determinant from ...	2003	12573588
efficient t cell repertoire selection in tetraparental chimeric mice independent of thymic epithelial mhc.	nonthymic epithelial cells were compared with thymic epithelial cells for their role in t cell repertoire selection. tetraparental aggregation chimeras were generated from t and b cell-deficient mice (h-2(d) scid or h-2(b) rag-/-) and thymus-deficient nude mice (h-2(b) or h-2(d)). these tetraparental mice showed primary protective cd8(+) t cell responses, after lymphocytic choriomeningitis virus infection, that were peptide-specifically restricted to either thymic or nonthymic epithelial mhc at ...	2003	12574503
pathogens of house mice on arid boullanger island and subantarctic macquarie island, australia.	studies on island populations of house mice (mus domesticus) and their viruses reveal insights into viral persistence in isolated communities. we surveyed the ectoparasites, endoparasites, and antiviral antibodies for 11 murine viruses and two bacteria of house mice inhabiting two islands off australia. house mice on boullanger island were seropositive to two viruses, murine cytomegalovirus and epizootic diarrhea of infant mice. on subantarctic macquarie island, house mice were seropositive for ...	2003	14733270
endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase ski-1/s1p.	the envelope glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv) is posttranslationally cleaved into two subunits. we show here that this endoproteolytic processing is not required for transport to the cell surface but is essential for lcmv gp to mediate infectivity of pseudotyped retroviral vectors. by systematic mutational analysis of the lcmv gp cleavage site, we determined that the consensus motif r-(r/k/h)-l-(a/l/s/t/f)(265) is essential for the endoproteolytic processing. in agr ...	2003	12584310
a new look at viruses in type 1 diabetes.	type 1 diabetes (t1d) results from the destruction of pancreatic beta cells. genetic factors are believed to be a major component for the development of t1d, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. viruses are one environmental factor that is implicated in the pathogenesis of t1d. to date, 14 different viruses have been reported to be associated with ...	2003	12592641
primary and secondary immunocompetence in mixed allogeneic chimeras.	targeted disruption of t cell costimulatory pathways, particularly cd28 and cd40, has allowed for the development of minimally myeloablative strategies for the induction of mixed allogeneic chimerism and donor-specific tolerance across full mhc barriers. in this study we analyze in depth the ability of mixed allogeneic chimeras in two strain combinations to mount effective host-restricted and donor-restricted antiviral cd4 and cd8 responses, as well as the impact of development of mixed chimeris ...	2003	12594261
cd4+ t cells are required for secondary expansion and memory in cd8+ t lymphocytes.	a long-standing paradox in cellular immunology concerns the conditional requirement for cd4+ t-helper (t(h)) cells in the priming of cytotoxic cd8+ t lymphocyte (ctl) responses in vivo. whereas ctl responses against certain viruses can be primed in the absence of cd4+ t cells, others, such as those mediated through 'cross-priming' by host antigen-presenting cells, are dependent on t(h) cells. a clearer understanding of the contribution of t(h) cells to ctl development has been hampered by the fa ...	2003	12594515
beta cell-specific cd80 (b7-1) expression disrupts tissue protection from autoantigen-specific ctl-mediated diabetes.	t cell responses toward pancreatic beta cell autoantigens arise spontaneously or on immunization in many mouse strains, yet sustained islet infiltration and progressive diabetes rarely ensues. most mouse diabetes models overcome the innocuous coexistence of anti-islet specific t cells and endogenous islets via incompletely understood mechanisms (e.g. the spontaneous disease onset of the non-obese diabetic mouse) or depend on overwhelming numbers of peripheral islet-specific t cells. we report th ...	2003	12604308
role of the virus nucleoprotein in the regulation of lymphocytic choriomeningitis virus transcription and rna replication.	the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) has a bisegmented negative-strand rna genome. each segment carries two viral genes in opposite orientation and separated by an intergenic region (igr). the rna-dependent rna polymerase (rdrp) l of lcmv produces subgenomic mrna and full-length genomic and antigenomic rna species in two different processes termed transcription and replication, respectively. it is widely accepted that intracellular nucleoprotein (np) levels regulat ...	2003	12610166
weak agonist self-peptides promote selection and tuning of virus-specific t cells.	recent progress has begun to define the interactions and signaling pathways that are triggered during positive selection. to identify and further examine self-peptides that can mediate positive selection, we searched a protein-database to find peptides that have minimal homology with the viral peptide (p33) that activates a defined p14 transgenic tcr. we identified four peptides that could bind the restriction element h-2d(b) and induce proliferation of p14 transgenic splenocytes at high concent ...	2003	12616489
cross-priming of cd8+ t cells stimulated by virus-induced type i interferon.	cd8+ t cell responses can be generated against antigens that are not expressed directly within antigen-presenting cells (apcs), through a process known as cross-priming. to initiate cross-priming, apcs must both capture extracellular antigen and receive specific activation signals. we have investigated the nature of apc activation signals associated with virus infection that stimulate cross-priming. we show that infection with lymphocytic choriomeningitis virus induces cross-priming by a mechani ...	2003	14502286
specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung.	having previously shown that previous immunity to one virus can influence the host response to a subsequent unrelated virus, we questioned whether the outcome to a given virus infection would be altered in similar or different ways by previous immunity to different viruses, and whether immunity to a given virus would have similar effects on all subsequent infections. in mouse models of respiratory viral infections, immunity to lymphocytic choriomeningitis virus (lcmv), murine cytomegalovirus (mc ...	2003	14507643
type i interferons promote cross-priming: more functions for old cytokines.		2003	14515123
myeloid marker expression on antiviral cd8+ t cells following an acute virus infection.	cd11b, cd11c, and f4/80 are normally used to define dendritic cell and/or macrophage populations. in this study, the expression of all three markers was observed on cd8(+) t cells following infection of mice with several distinct viruses. using lymphocytic choriomeningitis virus as a model virus, it was found that relatively more cd11b(+)cd8(+) and cd11c(+)cd8(+) t cells were present in the periphery than in primary lymphoid organs; in contrast, the f4/80(+)cd8(+) t cell population was more prev ...	2003	14515257
mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions.	the glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv) serves as virus attachment protein to its receptor on host cells and is a key determinant for cell tropism, pathogenesis, and epidemiology of the virus. the gp of lcmv is posttranslationally cleaved by the subtilase ski-1/s1p into two subunits, the peripheral gp1, which is implicated in receptor binding, and the transmembrane gp2 that is structurally similar to the fusion active membrane proximal portions of the glycoproteins of ...	2003	14517070
different dynamics of cd4+ and cd8+ t cell responses during and after acute lymphocytic choriomeningitis virus infection.	we fit a mathematical model to data characterizing the primary cellular immune response to lymphocytic choriomeningitis virus. the data enumerate the specific cd8(+) t cell response to six mhc class i-restricted epitopes and the specific cd4(+) t cell responses to two mhc class ii-restricted epitopes. the peak of the response occurs around day 8 for cd8(+) t cells and around day 9 for cd4(+) t cells. by fitting a model to the data, we characterize the kinetic differences between cd4(+) and cd8(+ ...	2003	14530309
selective depletion of nonspecific t cells during the early stage of immune responses to infection.	transient t cell depletion occurs before the development of an effective immune response to infection. in this study we show that most t cells, regardless of specificity, are induced to express early activation markers soon after infection with listeria monocytogenes or lymphocytic choriomeningitis virus. ag-specific t cells are further activated to display late activation markers and undergo extensive proliferation. as ag-specific t cells begin to expand, nonspecific t cells are depleted en mas ...	2003	14530360
the small ring finger protein z drives arenavirus budding: implications for antiviral strategies.	by using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv), we have identified the arenavirus small ring finger z protein as the main driving force of virus budding. both lcmv and lassa fever virus (lfv) z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the gag protein of rous sarcoma virus. lcmv and lfv z proteins contain proline-rich motifs that are characteristic of l ...	2003	14563923
interplay between tcr affinity and necessity of coreceptor ligation: high-affinity peptide-mhc/tcr interaction overcomes lack of cd8 engagement.	cd8 engagement is believed to be a critical event in the activation of naive t cells. in this communication, we address the effects of peptide-mhc (pmhc)/tcr affinity on the necessity of cd8 engagement in t cell activation of primary naive cells. using two peptides with different measured avidities for the same pmhc-tcr complex, we compared biochemical affinity of pmhc/tcr and the cell surface binding avidity of pmhc/tcr with and without cd8 engagement. we compared early signaling events and lat ...	2003	14568922
deficient cd4+ t cell priming and regression of cd8+ t cell functionality in virus-infected mice lacking a normal b cell compartment.	in this study, we investigate the state of t cell-mediated immunity in b cell-deficient (b(-/-)) mice infected with two strains of lymphocytic choriomeningitis virus known to differ markedly in their capacity to persist. in b(-/-) c57bl mice infected with the more persisting virus, virus-specific cd8(+) t cells are initially generated that are qualitatively similar to those in wild-type mice. however, although cell numbers are well sustained over time, the capacity to produce cytokines is rapidl ...	2003	14568949
antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies.	two gene-targeted immunoglobulin heavy chain transgenic mouse strains, tgh(kl25) and tgh(vi10), expressing neutralizing specificities for lymphocytic choriomeningitis virus and vesicular stomatitis virus, respectively, have been generated. three days after lymphocytic choriomeningitis virus infection, tgh(kl25) mice showed a thymus-independent neutralizing igm response followed by thymus-dependent (td) igg. in contrast, wt mice mounted only a td igg response around day 80. these observations ind ...	2003	14569006
the role of stat1 in viral sensitization to lps.	the phenomenon of endotoxin sensitization by virus infection is well documented but not yet well understood. infection by virtually any viral agent will quickly induce expression of type i interferons (ifn-alpha/beta), and type ii ifn-gamma production will follow as nk cells and t cells are activated. it has been well established that type ii ifn pretreatment can intensify the effects of endotoxin. we have recently demonstrated that type i ifn induction by lymphocytic choriomeningitis virus (lcm ...	2003	14577848
correction of bleeding diathesis without liver toxicity using arenaviral-pseudotyped hiv-1-based vectors in hemophilia a mice.	hemophilia a is an inheritable x-linked bleeding disorder most frequently occurring as a consequence of genetic alterations within the factor viii (fviii) gene. in the present study, pseudotyped human immunodeficiency virus type 1 (hiv-1)-derived lentivectors expressing hfviii were assessed for the ability to correct the hemophilia a phenotype in fviii knockout mice. therapeutic levels of plasma hfviii (1-7 ng/ml) were detected in c57b1/6 mice (4-5 weeks old) after portal vein administration of ...	2003	14577928
role of macrophage inflammatory protein-1alpha in t-cell-mediated immunity to viral infection.	the immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1alpha (mip-1alpha) was evaluated. generation of virus-specific effector t cells is unimpaired in mip-1alpha-deficient mice. furthermore, mip-1alpha is not required for t-cell-mediated virus control or virus-induced t-cell-dependent inflammation. thus, mip-1alpha is not mandatory for t-cell-mediated antiviral immunity.	2003	14581577
changing immunodominance patterns in antiviral cd8 t-cell responses after loss of epitope presentation or chronic antigenic stimulation.	the h-2(b)-restricted cd8 t-cell response against lymphocytic choriomeningitis virus is directed against at least 10 dominant and subdominant epitopes, including two newly identified epitopes in the nucleoprotein. we have used this set of epitopes to characterize the plasticity of the hierarchy under different experimental circumstances, i.e., loss of mhc class i molecules, loss of specific epitopes (ctl escape), and prolonged antigenic stimulation (chronic infection). we found that loss of epit ...	2003	14592762
control of effector cd8+ t cell function by the transcription factor eomesodermin.	activated cd8+ t cells play a critical role in host defense against viruses, intracellular microbes, and tumors. it is not clear if a key regulatory transcription factor unites the effector functions of cd8+ t cells. we now show that eomesodermin (eomes), a paralogue of t-bet, is induced in effector cd8+ t cells in vitro and in vivo. ectopic expression of eomes was sufficient to invoke attributes of effector cd8+ t cells, including interferon-gamma (ifn-gamma), perforin, and granzyme b. loss-of- ...	2003	14605368
immunodominance of an antiviral cytotoxic t cell response is shaped by the kinetics of viral protein expression.	lymphocytic choriomeningitis virus (lcmv) infection induces a protective ctl response consisting of gp- and nucleoprotein (np)-specific ctl. we find that a small load of lcmv led to immunodominance of np-ctl, whereas a large viral load resulted in dominance of gp-ctl. this is the first study describing that immunodominance is not fixed after infection with a given pathogen, but varies with the viral load instead. we assumed higher ag sensitivity for np-ctl, which would explain their preferential ...	2003	14607945
regulation of viral and autoimmune responses.	we have studied the induction and effector function of th2-like regulatory cells in mouse models for type 1 diabetes (nod and rip-lcmv). cd4+ lymphocytes with specificity for insulin can be induced by immunization with the insulin b chain via the oral route or by dna vaccination. such cells are protective upon adoptive transfer and prevent diabetes development in syngeneic pre-diabetic recipients. in comparison to non-regulatory insulin b-specific cell lines, they produce high amounts of interle ...	2003	14609223
selective expression of the interleukin 7 receptor identifies effector cd8 t cells that give rise to long-lived memory cells.	a major unanswered question is what distinguishes the majority of activated cd8 t cells that die after an acute viral infection from the small fraction (5-10%) that survive to become long-lived memory cells. in this study we show that increased expression of the interleukin 7 receptor alpha-chain (il-7ralpha) identifies the effector cd8 t cells that will differentiate into memory cells. il-7r(hi) effector cells contained increased amounts of antiapoptotic molecules, and adoptive transfer of il-7 ...	2003	14625547
efficient induction of cd8 t-associated immune protection by vaccination with mrna transfected dendritic cells.	dendritic cells are excellent targets for antigen-specific immune intervention. here we attempted to introduce a cd8 t cell-dependent epitope into dendritic cells for presentation on major histocompatibility complex class i and induction of immunity. murine bone-marrow-derived dendritic cells were subjected to electroporation with mrna transcribed in vitro from a plasmid encoding lymphocytic choriomeningitis virus glycoprotein or enhanced green fluorescent protein under the control of a t7 promo ...	2003	14632191
activation of antigen-specific cd8 t cells results in minimal killing of bystander bacteria.	memory cd8 t cells play a critical role in protective immunity against intracellular pathogens. in addition to their ability to specifically recognize and lyse infected targets, activated cd8 t cells secrete cytokines that induce phagocytic cells to engulf and kill bacterial pathogens. in this study, we asked whether activation of ag-specific cd8 t cells results in nonspecific killing of bystander bacteria during a mixed infection. mice with epitope-specific memory cd8 t cells were coinfected wi ...	2003	14634115
turning immunological memory into amnesia by depletion of dividing t cells.	immunological memory, defined as more efficient immune responses on antigen reexposure, can last for decades. the current paradigm is that memory is maintained by antigen-experienced "memory t cells" that can be long-lived quiescent or dividing. the contribution of t cell division to memory maintenance is poorly known and has important clinical implications. in this study, we directly addressed the role of dividing t cells in immunological memory maintenance by evaluating the consequences of the ...	2003	14634206
on the role of apc-activation for in vitro versus in vivo t cell priming.	professional antigen-presenting cells take up antigens for processing and presentation in association with mhc class i and ii molecules. when apcs receive the right stimuli, they undergo a maturation process and migrate to secondary lymphoid organs to trigger t cell activation. in this study, we compared side-by-side in vivo and in vitro activation of t cells. transgenic cd8(+) t cells specific for the p33 epitope, derived from the lymphocytic choriomeningitis virus glycoprotein, were labeled wi ...	2003	14643299
alpha-dystroglycan can mediate arenavirus infection in the absence of beta-dystroglycan.	dystroglycan (dg) is a highly versatile cell surface molecule that provides a molecular link between the extracellular matrix (ecm) and the actin-based cytoskeleton. encoded by a single gene, dg is posttranslationally processed to form alpha-dg, a peripheral protein identified as the cellular receptor for lymphocytic choriomeningitis virus (lcmv) and lassa fever virus (lfv), and the membrane-spanning subunit beta-dg. the link of beta-dg to the actin-based cytoskeleton and its association with th ...	2003	14644604
specific cytotoxic t cells eliminate cells producing neutralizing antibodies.		2003	14647387
targeting schwann cells by nonlytic arenaviral infection selectively inhibits myelination.	members of the arenavirus family, famous for their hemorrhagic syndromes, cause distinct neurological disorders; however, cellular and molecular targets as well as pathogenesis of peripheral nervous system disorders associated with these viruses are unknown. using noncytolytic lymphocytic choriomeningitis virus, the prototype arenavirus, and pseudotyped lassa fever virus, we showed that the schwann cells, but not the neurons, were preferentially targeted and harbored the virus. this permissivene ...	2003	14657400
cutting edge: stimulation with the cognate self-antigen induces expression of the ly49a receptor on self-reactive t cells which modulates their responsiveness.	nk cell self-tolerance is maintained by inhibitory receptors specific for mhc class i molecules. inhibitory nk receptors are also expressed on memory cd8 t cells but their biological relevance on t cells is unclear. in this study, we describe the expression of the ly49a receptor on a subset of autoreactive t cells which persist in mice double-transgenic for the lymphocytic choriomeningitis virus-derived peptide gp33 and a tcralphabeta specific for the gp33. no ly49a-expressing cells are found in ...	2003	14662829
among cxcr3 chemokines, ifn-gamma-inducible protein of 10 kda (cxc chemokine ligand (cxcl) 10) but not monokine induced by ifn-gamma (cxcl9) imprints a pattern for the subsequent development of autoimmune disease.	infection of the pancreas with lymphocytic choriomeningitis virus results in rapid and differential expression among cxcr3 chemokines. ifn-gamma-inducible protein of 10 kda (ip-10), in contrast with monokine induced by ifn-gamma and ifn-inducible t cell-alpha chemoattractant, is strongly expressed within 24 h postinfection. blocking of ip-10, but not monokine induced by ifn-gamma, aborts severity of ag-specific injury of pancreatic beta cells and abrogates type 1 diabetes. mechanistically, ip-10 ...	2003	14662890
antigen-driven effector cd8 t cell function regulated by t-bet.	type 1 immunity relies on the differentiation of two major subsets of t lymphocytes, the cd4+ t helper (th) cell and the cd8+ cytotoxic t cell, that direct inflammatory and cytotoxic responses essential for the destruction of intracellular and extracellular pathogens. in contrast to cd4 cells, little is known about transcription factors that control the transition from the cd8 naïve to effector cell stage. here, we report that the transcription factor t-bet, known to regulate th cell differentia ...	2003	14673093
an essential role of th1 responses and interferon gamma in infection-mediated suppression of neoplastic growth.	we had previously demonstrated that in mice acute toxoplasmosis leads to systemic inhibition of angiogenesis and, consequently, strong suppression of neoplastic growth. here we investigated the role of th1 cytokines, in particular interferon gamma (ifn-gamma), in this phenomenon. besides toxoplasma, neoplastic growth was readily blocked during acute infection with other th1 response-inducing pathogens such as listeria monocytogenes and lymphocytic choriomeningitis virus (lcmv). in contrast, chro ...	2003	14688478
your diagnosis, please. neonate with hydrocephalus.		2003	14700046
detection of lymphocytic choriomeningitis virus by use of fluorogenic nuclease reverse transcriptase-polymerase chain reaction analysis.	lymphocytic choriomeningitis virus (lcmv) induces persistent infections in laboratory mice; is a known contaminant of biological materials, such as transplantable tumor cell lines; and is of great concern in animal facilities due to its zoonotic potential. fluorogenic nuclease reverse transcriptase-polymerase chain reaction (fnrt-pcr) assays combine rt-pcr with an internal fluorogenic hybridization probe, thereby potentially enhancing specificity and eliminating post-pcr processing. an fnrt-pcr ...	2003	12625508
hypergammaglobulinemia and autoantibody induction mechanisms in viral infections.	polyclonal hypergammaglobulinemia is a characteristic of chronic inflammatory conditions, including persisting viral infections and autoimmune diseases. here we have studied hypergammaglobulinemia in mice infected with lymphocytic choriomeningitis virus (lcmv), which induces nonspecific immunoglobulins as a result of switching natural igm specificities to igg. the process is dependent on help from cd4+ t cells that specifically recognize lcmv peptides presented by b cells on major histocompatibi ...	2003	12627229
modelling the dynamics of lcmv infection in mice: ii. compartmental structure and immunopathology.	in this study, we develop a mathematical model for analysis of the compartmental aspects and immunopathology of lymphocytic choriomeningitis virus (lcmv) infection in mice. we used sets of original and published data on systemic (extrasplenic) virus distribution to estimate the parameters of virus growth and elimination for spleen and other anatomical compartments, such as the liver, kidney, thymus and lung as well as transfer rates between blood and the above organs. a mathematical model quanti ...	2003	12642113
viral persistence alters cd8 t-cell immunodominance and tissue distribution and results in distinct stages of functional impairment.	chronic viral infections often result in ineffective cd8 t-cell responses due to functional exhaustion or physical deletion of virus-specific t cells. however, how persisting virus impacts various cd8 t-cell effector functions and influences other aspects of cd8 t-cell dynamics, such as immunodominance and tissue distribution, remains largely unknown. using different strains of lymphocytic choriomeningitis virus (lcmv), we compared responses to the same cd8 t-cell epitopes during acute or chroni ...	2003	12663797
combinatorial immunoglobulin light chain variability creates sufficient b cell diversity to mount protective antibody responses against pathogen infections.	to analyze how combinatorial light (l) chain diversity influences the b cell repertoire, we studied mice with a homozygous immunoglobulin-heavy-chain null mutation (mu mt), in which the b cell developmental block was overridden by the expression of a transgenic immunoglobulin mu heavy (h) chain derived from a vesicular stomatitis virus indiana serotype (vsv-ind)-neutralizing ab (t11 mu mt mice). the randomly integrated transgene could not undergo secondary rearrangements and was expressed in com ...	2003	12672061
direct visualization of cross-reactive effector and memory allo-specific cd8 t cells generated in response to viral infections.	cd8 t cell cross-reactivity between heterologous viruses has been shown to provide protective immunity, induce immunopathology, influence the immunodominance of epitope-specific t cell responses, and shape the overall memory population. virus infections also induce cross-reactive allo-specific ctl responses. in this study, we quantified the allo-specific cd8 t cells elicited by infection of c57bl/6 (b6) mice with lymphocytic choriomeningitis virus (lcmv). cross-reactive lcmv-specific cd8 t cells ...	2003	12682237
requirement for cd4 t cell help in generating functional cd8 t cell memory.	although primary cd8 responses to acute infections are independent of cd4 help, it is unknown whether a similar situation applies to secondary responses. we show that depletion of cd4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory cd8 cells to reinfection. memory cd8 cells generated in cd4+/+ mice responded normally when transferred into cd4-/- hosts, whereas memory cd8 cells generated in cd4-/- mice mounted de ...	2003	12690201
therapeutic use of il-2 to enhance antiviral t-cell responses in vivo.	interleukin (il)-2 is currently used to enhance t-cell immunity but can have both positive and negative effects on t cells. to determine whether these opposing results are due to il-2 acting differently on t cells depending on their stage of differentiation, we examined the effects of il-2 therapy during the expansion, contraction and memory phases of the t-cell response in lymphocytic choriomeningitis virus (lcmv)-infected mice. il-2 treatment during the expansion phase was detrimental to the s ...	2003	12692546
lymphocytic choriomeningitis virus infection in a province of spain: analysis of sera from the general population and wild rodents.	lymphocytic choriomeningitis virus (lcmv) is a rodent-borne virus belonging to the family arenaviridae, genus arenavirus, which causes a wide spectrum of human disease. however, data on lcmv infection in spain is scant. to investigate whether this virus causes infection in spain, 400 serum samples from the general population (191 males, 209 females) and 100 from wild rodents were studied by immunofluorescence assay (ifa) using l-929 cells infected with lcmv. the study was performed in the "commu ...	2003	12696116
sensitizing antigen-specific cd8+ t cells for accelerated suicide causes immune incompetence.	death receptor-mediated activation-induced apoptosis of antigen-specific t cells is a major mechanism of peripheral tolerance induction and immune homeostasis. failure to undergo activation-induced cell death (aicd) is an important underlying cause of many autoimmune diseases. thus, enhancing the t cell's own suicide mechanism may provide an efficient therapy for the treatment of autoimmune diseases. bisindolylmaleimide viii (bis viii), a pkc inhibitor, can sensitize t cells for death receptor-i ...	2003	12697738
viral infection results in massive cd8+ t cell expansion and mortality in vaccinated perforin-deficient mice.	perforin-mediated cytotoxicity is essential for clearance of primary lcmv infection. balb/c-perforin-deficient (pko) mice survived lcmv infection by deleting np(118)-specific cd8(+) t cells whereas vaccination of pko mice with listeria expressing np(118) generated a stable memory cd8(+) t cell population. however, >85% of vaccinated balb/c-pko mice died after lcmv infection. mortality was associated with enormous expansion of np(118)-specific cd8(+) t cells in both lymphoid and nonlymphoid tissu ...	2003	12705850
lethal mutagenesis of the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv).	passage of the prototypic arenavirus lymphocytic choriomenigitis virus (lcmv) in cultured cells in the presence of the mutagenic agent 5-fluorouracil (fu) resulted in efficient and systematic virus extinction under conditions that did not significantly affect cell survival. fu-mediated extinction of lcmv was associated with 3.6- to 10-fold increases in the mutation frequencies for the three viral genes examined, but with only very modest effects on virus replication and transcription during a si ...	2003	12706088
mitochondrial potential and reactive oxygen intermediates in antigen-specific cd8+ t cells during viral infection.	following many viral infections, there are large expansions of ag-specific cd8(+) t cells. after viral clearance, mechanisms exist to ensure that the vast majority of effector cells undergo apoptosis. in studies of thymocyte apoptosis, loss of mitochondrial potential (deltapsi(m)) and excess production of reactive oxygen intermediates have been implicated as key events in cellular apoptosis. the purpose of the experiments presented in this work was to determine these parameters in ag-specific cd ...	2003	12707355
public versus personal serotypes of a viral quasispecies.	noncytopathic rna viruses persist in their natural hosts at various levels as highly mutating quasispecies. they exhibit only one known serotype. in most inbred dba2 mice infected with 2 x 10(4) or 2 x 10(6) plaque-forming units (pfu) of lymphocytic choriomeningitis virus (lcmv), the virus is transiently controlled below detectable levels measured with conventional assays (<1.7 pfu), but reemerges despite a common neutralizing ab (nab) response. wild-type virus and cloned mutant viruses that had ...	2003	12730366
expression of hepatitis c virus proteins inhibits interferon alpha signaling in the liver of transgenic mice.	background & aims hepatitis c virus (hcv) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. the majority of patients treated with interferon alpha do not have a sustained response with clearance of the virus. the molecular mechanisms underlying interferon resistance are poorly understood. interferon-induced activation of the jak-stat (signal transducer and activator of transcription) signal transduction pathway is essential for the induction of an anti ...	2003	12730885
regulation of cd8+ t cells undergoing primary and secondary responses to infection in the same host.	naive ag-specific cd8(+) t cells expand, contract, and become memory cells after infection and/or vaccination. memory cd8(+) t cells provide faster, more effective secondary responses against repeated exposure to the same pathogen. using an adoptive transfer system with low numbers of trackable nontransgenic memory cd8(+) t cells, we showed that secondary responses can be comprised of both primary (naive) and secondary (memory) cd8(+) t cells after bacterial (listeria monocytogenes) and/or viral ...	2003	12734336
clonal exhaustion as a result of immune deviation.	an overwhelming virus infection that spreads within a few days throughout the host can cause deletion of the specific cytotoxic t lymphocytes (ctl). this phenomenon is known as 'clonal exhaustion'. current explanations for this phenomenon are 'clonal', and consider either the terminal differentiation of the virus-specific ctl to an effector phenotype, or the lack of help and antigen presentation for a specific ctl clone. the virus remains controlled by some other form of immunity in the exhauste ...	2003	12749529
the cholera toxin b subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes.	when conjugated to various proteins, the nontoxic b-chain of cholera toxin (ctb) significantly increases the ability of these proteins to induce immunological tolerance after oral administration. here, we investigated if a nonconjugated form of ctb enhances the induction of immune tolerance after oral insulin administration. induction of immunological tolerance was studied after oral administration of insulin preparations in three mouse models; an insulin/ovalbumin coimmunization model, a model ...	2003	12753499
virus-specific cd8 t cells in peripheral tissues are more resistant to apoptosis than those in lymphoid organs.	cd8 t cells persist at high frequencies in peripheral organs after resolution of an immune response, and their presence in the periphery is important for resistance to secondary challenge. we show here that lcmv-specific t cells in peripheral tissue (peritoneal cavity, lung, fat pads) reacted much less with the apoptotic marker annexin-v than those in spleen and lymph nodes. this was not due to a tcr-based selection. in comparison to lymphoid tissue, t cells in the periphery expressed lower leve ...	2003	12753740
role of toll-like receptors in costimulating cytotoxic t cell responses.	stimulation of toll-like receptors (tlr) by pathogen-derived compounds leads to activation of apc, facilitating the induction of protective immunity. this phenomenon is the basis of most adjuvant formulations currently in development. here, we tested the ability of tlr2, 3, 4, 5, 7 and 9 signaling to enhance ctl responses upon vaccination with virus-like particles. stimulation of tlr2 and 4 failed to increase ctl responses, whereas ligands for tlr3, 5 and 7 exhibited moderate adjuvant function. ...	2003	12778463
infection of dendritic cells by lymphocytic choriomeningitis virus.	dendritic cells (dcs) comprise the major antigen-presenting cells (apcs) of the host, uniquely programmed to stimulate immunologically naïve t lymphocytes. viruses that can target and disorder the function of these cells enjoy a selective advantage. the cellular receptor for lymphocytic choriomeningitis virus (lcmv), lassa fever virus (lfv), and several other arenaviruses is alpha-dystroglycan (alpha-dg). among cells of the immune system, cd11c+ and dec-205+ dcs primarily and preferentially expr ...	2003	12797446
the virus-encoded chemokine vmip-ii inhibits virus-induced tc1-driven inflammation.	the human herpesvirus 8-encoded protein vmip-ii is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of t cells with a type 1 cytokine profile. for the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit virus-induced t-cell-mediated inflammation. this was done by use of the well-established model system murine lymphocytic choriomeningitis virus infection. mice were infected in the footpad, and the in ...	2003	12805438
recombinant lymphocytic choriomeningitis virus expressing vesicular stomatitis virus glycoprotein.	a recombinant s segment rna (sr) of the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) where the glycoprotein of vesicular stomatitis virus (vsvg) was substituted for the glycoprotein of lcmv (lcmv-gp) was produced intracellularly from cdna under the control of a polymerase i promoter. coexpression of the lcmv proteins np and l allowed expression of vsvg from sr. infection of transfected cells with wt lcmv (lcmvwt) resulted in reassortment of the l segment of lcmvwt with the sr ...	2003	12808132
"bystander" recruitment of systemic memory t cells delays the immune response to respiratory virus infection.	the concept of heterologous t cell immunity postulates that nonspecific memory t cells recruited and reactivated in the context of an unrelated virus infection may contribute to protective antiviral immunity. pulmonary infection with respiratory syncytial virus (rsv) of mice immune to lymphocytic choriomeningitis virus (lcmv) leads to substantial recruitment of systemic lcmv-specific memory cd8 t cells to the lung. using a sensitive tcr-transgenic model, we show that such "bystander" recruitment ...	2003	12811844
cutting edge: rapid in vivo killing by memory cd8 t cells.	in this study, we examined the cytotoxic activity of effector and memory cd8 t cells in vivo. at the peak of the ctl response following an acute lymphocytic choriomeningitis virus infection, effector cd8 t cells exhibited extremely rapid killing and started to eliminate adoptively transferred target cells within 15 min by a perforin-dependent mechanism. although resting memory cd8 t cells are poorly cytolytic by in vitro (51)cr release assays, there was rapid elimination (within 1-4 h) of target ...	2003	12816979
viral infection switches non-plasmacytoid dendritic cells into high interferon producers.	type i interferons (ifn-i) are important cytokines linking innate and adaptive immunity. plasmacytoid dendritic cells make high levels of ifn-i in response to viral infection and are thought to be the major source of the cytokines in vivo. here, we show that conventional non-plasmacytoid dendritic cells taken from mice infected with a dendritic-cell-tropic strain of lymphocytic choriomeningitis virus make similarly high levels of ifn-i on subsequent culture. similarly, non-plasmacytoid dendritic ...	2003	12819664
involvement of mkk6 in tcralphabeta(int)cd69lo: a target population for apoptotic cell death in thymocytes.	by analyzing real-time caspase activity and dna fragmentation in live thymocytes, we found that apoptosis occurs predominantly in a tcralphabeta(int)/hicd69lo population. the number of caspase-active cells and dna-fragmented cells in mkk6-deficient mice, which were originally generated in our laboratory by gene targeting, was decreased in the tcralphabeta(int)cd69lo population but not in the tcralphabetahicd69lo population. the percentage of caspase-active cells in the h-y-specific tcrint popula ...	2003	12824301
attrition of virus-specific memory cd8+ t cells during reconstitution of lymphopenic environments.	viruses can cause a severe lymphopenia early in infection and a subsequent, lasting loss of pre-existing cd8(+) memory t cells. we therefore questioned how well virus ag-specific memory cd8(+) t cells could reconstitute mice rendered lymphopenic as a consequence of genetics, irradiation, or viral or poly(i:c)-induced cytokines. in each case, reconstitution of the cd8(+) compartment was associated with limited division of virus-specific memory t cells and a reduction in their proportion. this ind ...	2003	12847230
innate immunity together with duration of antigen persistence regulate effector t cell induction.	proliferation of t cells is important for the expansion of specific t cell clones during immune responses. in addition, for the establishment of protective immunity against viruses, bacteria, and tumors, the expanded t cells must differentiate into effector t cells. here we show that effector t cell generation is driven by activation of apcs and duration of antigenic stimulation. adoptively transferred tcr-transgenic t cells extensively proliferated upon immunization. however, these t cells fail ...	2003	12847247
absence of preproenkephalin increases the threshold for t cell activation.	certain forms of the neuroendocrine hormone preproenkephalin (ppnk) are produced by t cells, b cells and macrophages. this hormone has been shown to be important in regulating a variety of immune responses; however, the basic mechanisms of this regulation are unknown. here we examine the ability of cd8 and cd4 ppnk-deficient t lymphocytes to proliferate to antigenic and mitogenic stimuli. we found that lymphocyte activation and proliferation to suboptimal concentrations of both anti-cd3 and anti ...	2003	12864972
viral meningitis and encephalitis: traditional and emerging viral agents.	in the united states, the annual number of central nervous system (cns) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. the recent incursion of west nile virus (wnv) into north america has led to a dramatic change in the incidence and epidemiology of summer-associated viral cns disease. as a result of increased testing for wnv, lesser known viral causes of cns infection have been identified. even the epidem ...	2003	12881794
diabetogenic potential of human pathogens uncovered in experimentally permissive beta-cells.	pancreatic beta-cell antiviral defense plays a critical role in protection from coxsackievirus b4 (cvb4)-induced diabetes. in the present study, we tested the hypothesis that interferon (ifn)-induced antiviral defense determines beta-cell survival after infection by the human pathogen cvb3, cytomegalovirus (cmv), and lymphocytic choriomeningitis virus (lcmv). we demonstrated that mice harboring beta-cells that do not respond to ifn because of the expression of the suppressor of cytokine signalin ...	2003	12882919
enhanced t cell responses due to diacylglycerol kinase zeta deficiency.	much is known about how t cell receptor (tcr) engagement leads to t cell activation; however, the mechanisms terminating tcr signaling remain less clear. diacylglycerol, generated after tcr ligation, is essential in t cells. its function must be controlled tightly to maintain normal t cell homeostasis. previous studies have shown that diacylglycerol kinase zeta (dgkzeta), which converts diacylglycerol to phosphatidic acid, can inhibit tcr signaling. here we show that dgkzeta-deficient t cells ar ...	2003	12883552
incomplete effector/memory differentiation of antigen-primed cd8+ t cells in gene gun dna-vaccinated mice.	dna vaccination is an efficient way to induce cd8+ t cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. to study this, we induced cd8+ memory responses directed towards defined viral epitopes, using dna vaccines encoding immunodominant mhc class i-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. this vaccine construct primed for a stronger recall response than did a more conventional minigene con ...	2003	12884860
protection against ctl escape and clinical disease in a murine model of virus persistence.	ctl escape mutations have been identified in several chronic infections, including mice infected with mouse hepatitis virus strain jhm. one outstanding question in understanding ctl escape is whether a cd8 t cell response to two or more immunodominant ctl epitopes would prevent ctl escape. although ctl escape at multiple epitopes seems intuitively unlikely, ctl escape at multiple cd8 t cell epitopes has been documented in some chronically infected individual animals. to resolve this apparent con ...	2003	12902505
long-lived signal peptide of lymphocytic choriomeningitis virus glycoprotein pgp-c.	signal peptides (sps) direct nascent secretory and membrane proteins to the membrane of the endoplasmic reticulum. they are usually cleaved from the nascent polypeptide by signal peptidase and then further proteolytically processed. the sp of the pre-glycoprotein (pgp-c) of the lymphocytic choriomeningitis virus spgp-c (signal peptide of pgp-c) shows different properties: 1) the spgp-c is unusually long (58 amino acid residues) and contains two hydrophobic segments interrupted by a lysine residu ...	2003	12917426
the b7 family member b7-h3 preferentially down-regulates t helper type 1-mediated immune responses.	we investigated the in vivo function of the b7 family member b7-h3 (also known as b7rp-2) by gene targeting. b7-h3 inhibited t cell proliferation mediated by antibody to t cell receptor or allogeneic antigen-presenting cells. b7-h3-deficient mice developed more severe airway inflammation than did wild-type mice in conditions in which t helper cells differentiated toward type 1 (t(h)1) rather than type 2 (t(h)2). b7-h3 expression was consistently enhanced by interferon-gamma but suppressed by int ...	2003	12925852
cutting edge: cross-presentation as a mechanism for efficient recruitment of tumor-specific ctl to the brain.	the number and localization of effector cells to the tumor site are crucial elements for immune rejection of solid tumors. however, for cerebral malignancies, antitumor responses need to be finely tuned to avoid neuropathologic consequences. in this study, we determine factors that regulate ctl localization and tumoricidal function after intracerebral implantation of tumors expressing model ag. h-2(bxd) mice implanted with a cw3(+) murine glioma lacking h-2k(d) molecules necessary to present the ...	2003	12928361
a transgenic mouse model genetically tags all activated cd8 t cells.	identifying and characterizing ag-specific cd8+ t cells are central to the study of immunological memory. although powerful strategies such as mhc tetramers and peptide-induced cytokine production assays exist for identifying ag-specific cd8+ t cells, alternate strategies that are not dependent upon a priori knowledge of the immunodominant and subdominant antigenic epitopes, as well as the mhc background of the animal are of obvious utility. in this study, we present a transgenic mouse model tha ...	2003	12928386
tcr binding kinetics measured with mhc class i tetramers reveal a positive selecting peptide with relatively high affinity for tcr.	the interaction between tcr and peptide-mhc (pmhc) complexes is crucial for the activation of t cells as well as for positive and negative selection in the thymus. the kinetics and affinity of this interaction and the densities of tcr and pmhc complexes on the cell surface are determining factors for different outcomes during thymic selection. in general, it is thought that agonist pmhc, which cause negative selection, have higher affinities and, in particular, slower off-rates than partial or w ...	2003	12928390
the bcl-2 family pro-apoptotic molecule, bnip3 regulates activation-induced cell death of effector cytotoxic t lymphocytes.	bnip3 is a recently described pro-apoptotic member of the bcl-2 family and in bnip3 cdna-transfected cell lines, cell death occurs via a caspase-independent pathway with opening of the mitochondrial permeability transition (pt) pore and rapid loss of mitochondrial transmembrane potential (delta psi m). however, its expression or function in physiologic cell types is not known. our results using the t-cell receptor transgenic mice p14, specific for lymphocyte choreomeningitis virus (lcmv) glycopr ...	2003	12941136
expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated t cells.	adhesive interactions are crucial to cell migration into inflammatory sites. using murine lymphocytic choriomeningitis virus as an ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory t cells. using this system and mhc tetramers to define ag-specific t cells, we demonstrate that contrary to being vlas, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated t ...	2003	12960301
measles virus infection induces chemokine synthesis by neurons.	the role that neurons play in the induction of the immune response following cns viral infection is poorly understood, largely owing to the belief that these cells are immunologically quiescent. in this report, we show that virus infection of neurons results in the synthesis of proinflammatory chemokines, which are early and important mediators of leukocyte recruitment to sites of viral infection. for these studies, a transgenic mouse model of neuron-restricted measles virus (mv) infection was u ...	2003	12960336
lassa virus z protein is a matrix protein and sufficient for the release of virus-like particles [corrected].	lassa virus is an enveloped virus with glycoprotein spikes on its surface. it contains an rna ambisense genome that encodes the glycoprotein precursor gp-c, the nucleoprotein np, the polymerase l, and the z protein. here we demonstrate that the lassa virus z protein (i). is abundant in viral particles, (ii). is strongly membrane associated, (iii). is sufficient in the absence of all other viral proteins to release enveloped particles, and (iv). contains two late domains, ptap and ppxy, necessary ...	2003	12970458
complement component 3 is required for optimal expansion of cd8 t cells during a systemic viral infection.	in addition to its established role in innate immune mechanisms, complement component c3 is also of critical importance in b cell activation and t cell-dependent ab responses. in this study, we have examined the requirement for c3 in the generation of primary cd8 t cell responses to an acute systemic viral infection. we compared ag-specific cd8 t cell responses to lymphocytic choriomeningitis virus (lcmv) between wild-type (+/+) and c3-deficient (c3(-/-)) mice on both 129/b6 and b6 backgrounds. ...	2003	12517942
arenavirus-mediated liver pathology: acute lymphocytic choriomeningitis virus infection of rhesus macaques is characterized by high-level interleukin-6 expression and hepatocyte proliferation.	lymphocytic choriomeningitis virus (lcmv) and lassa virus can cause hemorrhagic fever and liver disease in primates. the we strain of lcmv (lcmv-we) causes a fatal lassa fever-like disease in rhesus macaques and provides a model for arenavirus pathogenesis in humans. lcmv-we delivered intravenously or intragastrically to rhesus macaques targets hepatocytes and induces high levels of liver enzymes, interleukin-6 (il-6), soluble il-6 receptor (sil-6r), and soluble tumor necrosis factor receptors ( ...	2003	12525606
sap is required for generating long-term humoral immunity.	long-lived plasma cells and memory b cells are the primary cellular components of long-term humoral immunity and as such are vitally important for the protection afforded by most vaccines. the sap gene has been identified as the genetic locus responsible for x-linked lymphoproliferative disease, a fatal immunodeficiency. mutations in sap have also been identified in some cases of severe common variable immunodeficiency disease. the underlying cellular basis of this genetic disorder remains uncle ...	2003	12529646
preferential escape of subdominant cd8+ t cells during negative selection results in an altered antiviral t cell hierarchy.	negative selection is designed to purge the immune system of high-avidity, self-reactive t cells and thereby protect the host from overt autoimmunity. in this in vivo viral infection model, we show that there is a previously unappreciated dichotomy involved in negative selection in which high-avidity cd8(+) t cells specific for a dominant epitope are eliminated, whereas t cells specific for a subdominant epitope on the same protein preferentially escape deletion. although this resulted in signif ...	2003	12538681
autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive.	pancreatic islets of langerhans are enveloped by peri-islet schwann cells (psc), which express glial fibrillary acidic protein (gfap) and s100beta. psc-autoreactive t- and b-cell responses arise in 3- to 4-week-old diabetes-prone non-obese diabetic (nod) mice, followed by progressive psc destruction before detectable beta-cell death. humans with probable prediabetes generate similar autoreactivities, and autoantibodies in islet-cell autoantibody (lca) -positive sera co-localize to psc. moreover, ...	2003	12539039
transcriptional and posttranscriptional control of hepatitis b virus gene expression.	hepatitis b virus (hbv) infects humans and certain nonhuman primates. viral clearance and acute disease are associated with a strong, polyclonal, multispecific cytotoxic t lymphocyte response. infiltrating t cells, as well as other activated inflammatory cells, produce cytokines that can regulate hepatocellular gene expression. using an hbv transgenic mouse model, our laboratory has previously demonstrated that adoptive transfer of hbv-specific cytotoxic t lymphocytes or injection of il-2 can no ...	2003	12552098
lineage relationship and protective immunity of memory cd8 t cell subsets.	memory cd8 t cells can be divided into two subsets, central (t(cm)) and effector (t(em)), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. our results show that t(cm) have a greater capacity than t(em) to persist in vivo and are more efficient in mediating protective immunity because of their increased proliferative potential. we also demonstrate that, following antigen clearance, t(em) convert to t(cm) and that the duration of ...	2003	12563257
induction of telomerase activity and maintenance of telomere length in virus-specific effector and memory cd8+ t cells.	acute viral infections induce extensive proliferation and differentiation of virus-specific cd8+ t cells. one mechanism reported to regulate the proliferative capacity of activated lymphocytes is mediated by the effect of telomerase in maintaining the length of telomeres in proliferating cells. we examined the regulation of telomerase activity and telomere length in naive cd8+ t cells and in virus-specific cd8+ t cells isolated from mice infected with lymphocytic choriomeningitis virus. these st ...	2003	12496394
ablation of cd8 and cd4 t cell responses by high viral loads.	to evaluate the impact of sustained viral loads on anti-viral t cell responses we compared responses that cleared acute lymphocytic choriomeningitis virus infection with those that were elicited but could not resolve chronic infection. during acute infection, as replicating virus was cleared, cd8 t cell responses were down-regulated, and a pool of resting memory cells developed. in chronically infected hosts, the failure to control the infection was associated with pronounced and prolonged activ ...	2003	12496434
cure of prediabetic mice by viral infections involves lymphocyte recruitment along an ip-10 gradient.	viruses can cause but can also prevent autoimmune disease. this dualism has certainly hampered attempts to establish a causal relationship between viral infections and type 1 diabetes (t1d). to develop a better mechanistic understanding of how viruses can influence the development of autoimmune disease, we exposed prediabetic mice to various viral infections. we used the well-established nod and transgenic rip-lcmv models of autoimmune diabetes. in both cases, infection with the lymphocytic chor ...	2004	14702111
effects of an epitope-specific cd8+ t-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants.	both cd4(+) and cd8(+) t cells are required for clearance of the murine coronavirus mouse hepatitis virus (mhv) during acute infection. we investigated the effects of an epitope-specific cd8(+) t-cell response on acute infection of mhv, strain a59, in the murine cns. mice with cd8(+) t cells specific for gp33-41 (an h-2d(b)-restricted cd8(+) t-cell epitope derived from lymphocytic choriomeningitis glycoprotein) were infected with a recombinant mhv-a59, also expressing gp33-41, as a fusion protei ...	2004	14722270
effect of chronic viral infection on epitope selection, cytokine production, and surface phenotype of cd8 t cells and the role of ifn-gamma receptor in immune regulation.	regulation of cd8 t cell responses in chronic viral infections is not well understood. in this study, we have compared the cd8 t cell responses to immunodominant and subdominant epitopes during an acute and a chronic lymphocytic choriomeningitis virus (lcmv) infection in mice. the epitope hierarchy of the primary cd8 t cell response was similar in acute and chronic lcmv infections. however, strikingly, the epitope hierarchy of the primary cd8 t cell response was conserved in the t cell memory on ...	2004	14734726
ifn-gamma promotes fas ligand- and perforin-mediated liver cell destruction by cytotoxic cd8 t cells.	to study liver cell damage by ctl, cd8 t cells from p14 tcr transgenic (tg) mice specific for the gp33 epitope of lymphocytic choriomeningitis virus with either deficiency in ifn-gamma (p14.ifn-gamma(null)), functional fas ligand (p14.gld), or perforin (p14.pko) were transferred into h8 tg mice ubiquitously expressing gp33 ag. treatment of h8 recipient mice with agonistic anti-cd40 abs induced vigorous expansion of the transferred p14 t cells and led to liver cell destruction determined by incre ...	2004	14734739