Publications

differential regulation of interferon regulatory factor (irf)-7 and irf-9 gene expression in the central nervous system during viral infection.	interferon regulatory factors (irfs) are a family of transcription factors involved in the regulation of the interferons (ifns) and other genes that may have an essential role in antiviral defense in the central nervous system, although this is currently not well defined. therefore, we examined the regulation of irf gene expression in the brain during viral infection. several irf genes (irf-2, -3, -5, -7, and -9) were expressed at low levels in the brain of uninfected mice. following intracrania ...	2005	15919906
lymphocytic choriomeningitis virus infection in organ transplant recipients--massachusetts, rhode island, 2005.	on may 3, 2005, cdc received a report of severe illness in four patients who had received solid organ transplants from a common donor. all four organ recipients subsequently were found to have evidence of infection with lymphocytic choriomeningitis virus (lcmv), a rodent-borne old world arenavirus. preliminary findings from the ensuing investigation indicate the source of infection likely was an infected hamster in the donor's home. this report summarizes the ongoing investigation and provides i ...	2005	15931158
rapid destruction of the tumor microenvironment by ctls recognizing cancer-specific antigens cross-presented by stromal cells.	a single tumor contains a heterogeneous population of cancer cells. some cancer cells express antigens and are susceptible to specific ctls. however, other cancer cells are antigen-loss variants (alvs) that escape these ctls because they express little or no antigen. here, we show that antigen-specific t cells can eliminate alvs when the parental population expresses a model gp33 antigen (kavynfatm) at a level sufficient to be locally cross-presented by the nonmalignant stromal cells. that is, t ...	2005	15934727
in vivo modulation of t cell responses and protective immunity by tcr antagonism during infection.	infectious agents are known to express altered peptide ligands that antagonize t cells in vitro; however, direct evidence of tcr antagonism during infection is still lacking, and its importance in the context of infection remains to be established. in this study, we used a murine model of infection with recombinant listeria monocytogenes and addressed three issues that are critical for assessing the role of tcr antagonism in the modulation of the immune response. first, we demonstrated that the ...	2005	15944303
il-7 receptor alpha chain expression distinguishes functional subsets of virus-specific human cd8+ t cells.	virus-specific cd8+ t cells emerge after infection with herpesviruses and maintain latency to these persistent pathogens. it has been demonstrated that murine memory cd8+ t-cell precursors specific for acute lymphocytic choriomeningitis virus express interleukin-7 receptor alpha (il-7ralpha), and il-7 is involved in maintaining memory populations after the clearance of antigen. to investigate whether human cd8+ t cells reactive toward persistent viruses are maintained similarly, we analyzed il-7 ...	2005	15947093
innate stat1-dependent genomic response of neurons to the antiviral cytokine alpha interferon.	alpha/beta interferons (ifns-alpha/beta) are cytokines that play an essential role in the host defense against viral infection. our previous studies have shown that the key ifn signaling molecule stat1 is highly elevated and activated in central nervous system neurons during viral infection and in transgenic mice with astrocyte production of ifn-alpha (glial fibrillary acidic protein [gfap]-ifn-alpha), suggesting that neurons are a very responsive target cell population for ifns. to elucidate th ...	2005	15956575
how viral infections affect the autoimmune process leading to type 1 diabetes.	despite a large body of evidence describing associations between viruses and the development of type 1 diabetes (t1d) in genetically prone individuals, clearly defining causative infectious agents has not been successful. a likely explanation is that the link between infections and autoimmunity is more multifaceted than we initially assumed. viral footprints might be hard to detect systemically or in the target organ once autoimmunity has been initiated, and several infections might have to act ...	2005	15963965
cd8alpha+ dendritic cells selectively present mhc class i-restricted noncytolytic viral and intracellular bacterial antigens in vivo.	cd8alpha(+) dendritic cells (dcs) have been shown to be the principal dc subset involved in priming mhc class i-restricted ctl immunity to a variety of cytolytic viruses, including hsv type 1, influenza, and vaccinia virus. whether priming of ctls by cd8alpha(+) dcs is limited to cytolytic viruses, which may provide dead cellular material for this dc subset, or whether these dcs selectively present intracellular ags, is unknown. to address this question, we examined ag presentation to a noncytol ...	2005	15972648
low cd8 t-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination.	therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. however, many therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral t-cell responses is not always observed. to examine these issues, we studied the impact of therapeutic vaccination, using a murine model of chronic infection with lymphocytic choriomeningitis virus (lcmv). our results demonstrate that therapeutic vaccination ...	2005	15994790
cross-presentation of the long-lived lymphocytic choriomeningitis virus nucleoprotein does not require neosynthesis and is enhanced via heat shock proteins.	many viral proteins that contain mhc class i-restricted peptides are long-lived, and it is elusive how they can give rise to class i epitopes. recently, we showed that direct presentation of an epitope of the long-lived lymphocytic choriomeningitis virus nucleoprotein (lcmv-np) required neosynthesis in accordance with the defective ribosomal products hypothesis. in this study, we report that lcmv-np can be cross-primed in mice using either lcmv-np-transfected human hek293 or balb/c-derived b8 ce ...	2005	16002676
immunoproteasome-deficient mice mount largely normal cd8+ t cell responses to lymphocytic choriomeningitis virus infection and dna vaccination.	during viral infection, constitutive proteasomes are largely replaced by immunoproteasomes, which display distinct cleavage specificities, resulting in different populations of potential cd8(+) t cell epitope peptides. immunoproteasomes are believed to be important for the generation of many viral cd8(+) t cell epitopes and have been implicated in shaping the immunodominance hierarchies of cd8(+) t cell responses to influenza virus infection. however, it remains unclear whether these conclusions ...	2005	16002717
role of thymic output in regulating cd8 t-cell homeostasis during acute and chronic viral infection.	although it is well documented that cd8 t cells play a critical role in controlling chronic viral infections, the mechanisms underlying the regulation of cd8 t-cell responses are not well understood. using the mouse model of an acute and chronic lymphocytic choriomeningitis virus (lcmv) infection, we have examined the relative importance of peripheral t cells and thymic emigrants in the elicitation and maintenance of cd8 t-cell responses. virus-specific cd8 t-cell responses were compared between ...	2005	16014905
inhibition, escape, and attenuated growth of severe acute respiratory syndrome coronavirus treated with antisense morpholino oligomers.	the recently emerged severe acute respiratory syndrome coronavirus (sars-cov) is a potent pathogen of humans and is capable of rapid global spread. peptide-conjugated antisense morpholino oligomers (p-pmo) were designed to bind by base pairing to specific sequences in the sars-cov (tor2 strain) genome. the p-pmo were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral rna motifs and secondary structures. several virus-targeted p ...	2005	16014928
impaired virus control and severe cd8+ t-cell-mediated immunopathology in chimeric mice deficient in gamma interferon receptor expression on both parenchymal and hematopoietic cells.	bone marrow chimeras were used to determine the cellular target(s) for the antiviral activity of gamma interferon (ifn-gamma). by transfusing such mice with high numbers of naive virus-specific cd8(+) t cells, a system was created in which the majority of virus-specific cd8(+) t cells would be capable of responding to ifn-gamma, but expression of the relevant receptor on non-t cells could be experimentally controlled. only when the ifn-gamma receptor is absent on both radioresistant parenchymal ...	2005	16014969
isg15, an interferon-stimulated ubiquitin-like protein, is not essential for stat1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus.	isg15 is an interferon-induced ubiquitin-like modifier which can be conjugated to distinct, but largely unknown, proteins. isg15 has been implicated in a variety of biological activities, which encompass antiviral defense, immune responses, and pregnancy. mice lacking ubp43 (usp18), the isg15-deconjugating enzyme, develop a severe phenotype with brain injuries and lethal hypersensitivity to poly(i:c). it has been reported that an augmented conjugation of isg15 in the absence of ubp43 induces pro ...	2005	16024773
opposing effects of cxcr3 and ccr5 deficiency on cd8+ t cell-mediated inflammation in the central nervous system of virus-infected mice.	t cells play a key role in the control of viral infection in the cns but may also contribute to immune-mediated cell damage. to study the redundancy of the chemokine receptors cxcr3 and ccr5 in regulating virus-induced cd8+ t cell-mediated inflammation in the brain, cxcr3/ccr5 double-deficient mice were generated and infected intracerebrally with noncytolytic lymphocytic choriomeningitis virus. because these chemokine receptors are mostly expressed by overlapping subsets of activated cd8+ t cell ...	2005	16034118
mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence.	enhanced mutagenesis may result in rna virus extinction, but the molecular events underlying this process are not well understood. here we show that 5-fluorouracil (fu)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (lcmv) resulted in preextinction populations whose consensus genomic nucleotide sequence remained unaltered. furthermore, fitness recovery passages in the absence of fu, or alternate virus passages in the presence and absence of fu, led to profound differenc ...	2005	16051837
intrinsic functional dysregulation of cd4 t cells occurs rapidly following persistent viral infection.	effective t-cell responses are critical to eradicate acute viral infections and prevent viral persistence. emerging evidence indicates that robust, early cd4 t-cell responses are important in effectively sustaining cd8 t-cell activity. herein, we illustrate that virus-specific cd4 t cells are functionally inactivated early during the transition into viral persistence and fail to produce effector cytokines (i.e., interleukin-2 and tumor necrosis factor alpha), thereby compromising an efficient an ...	2005	16051844
interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with rodents.	in may 2005, cdc received reports of four organ-transplant recipients with unknown illness. all were discovered to have been infected with lymphocytic choriomeningitis virus (lcmv) via a common organ donor. epidemiologic investigation traced the source of the virus to a pet hamster purchased by the donor from a local pet store. lcmv testing of other rodents at the pet store revealed three other lcmv-infected rodents (two hamsters and a guinea pig), supplied by a single distributor (distributor a ...	2005	16079740
rna interference-mediated virus clearance from cells both acutely and chronically infected with the prototypic arenavirus lymphocytic choriomeningitis virus.	several arenaviruses, including lassa fever virus, cause severe, often lethal hemorrhagic fever in humans. no licensed vaccines are available in the united states, and currently there is no efficacious therapy to treat this viral infection. therefore the importance of developing effective antiviral approaches to combat pathogenic arenaviruses is clear. moreover, the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is an important model for the study of viral persistence and associ ...	2005	16103158
update: interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with pet rodents.	in may 2005, cdc received reports of illness in four solid-organ transplant recipients who were later determined to have been infected with lymphocytic choriomeningitis virus (lcmv) from a common organ donor. three of the four organ recipients died, 23-27 days after transplantation. this report updates information about the ongoing investigation and provides interim measures for reducing the risk for lcmv infection from pet rodents associated with this outbreak.	2005	16107785
in vivo generation of pathogen-specific th1 cells in the absence of the ifn-gamma receptor.	the precise mechanisms that govern the commitment of cd4 t cells to become th1 or th2 cells in vivo are incompletely understood. recent experiments demonstrate colocalization of the ifn-gammar chains with the tcr during activation of naive cd4 t cells, suggesting that association of these molecules may be involved in determining lineage commitment. to test the role of ifn-gamma and its receptor in the generation of th1 ag-specific cd4 t cells, we analyzed mice after infection with listeria monoc ...	2005	16116201
immunomodulatory dendritic cells require autologous serum to circumvent nonspecific immunosuppressive activity in vivo.	in immunotherapy, dendritic cells (dcs) can be used as powerful antigen-presenting cells to enhance or suppress antigen-specific immunity upon in vivo transfer in mice or humans. however, to generate sufficient numbers of dcs, most protocols include an ex vivo culture step, wherein the cells are exposed to heterologous serum and/or antigenic stimuli. in mouse models of virus infection and virus-induced autoimmunity, we tested how heterologous serum affects the immunomodulatory capacity of immatu ...	2005	16118326
type i interferons act directly on cd8 t cells to allow clonal expansion and memory formation in response to viral infection.	t cell expansion and memory formation are generally more effective when elicited by live organisms than by inactivated vaccines. elucidation of the underlying mechanisms is important for vaccination and therapeutic strategies. we show that the massive expansion of antigen-specific cd8 t cells that occurs in response to viral infection is critically dependent on the direct action of type i interferons (ifn-is) on cd8 t cells. by examining the response to infection with lymphocytic choriomeningiti ...	2005	16129706
increased expression of the nk cell receptor klrg1 by virus-specific cd8 t cells during persistent antigen stimulation.	the killer cell lectin-like receptor g1 (klrg1) is a natural killer cell receptor expressed by t cells that exhibit impaired proliferative capacity. here, we determined the klrg1 expression by virus-specific t cells. we found that repetitive and persistent antigen stimulation leads to an increase in klrg1 expression of virus-specific cd8+ t cells in mice and that virus-specific cd8+ t cells are mostly klrg1+ in chronic human viral infections (human immunodeficiency virus, cytomegalovirus, and ep ...	2005	16140789
islet-specific expression of cxcl10 causes spontaneous islet infiltration and accelerates diabetes development.	during inflammation, chemokines are conductors of lymphocyte trafficking. the chemokine cxcl10 is expressed early after virus infection. in a virus-induced mouse model for type 1 diabetes, cxcl10 blockade abrogated disease by interfering with trafficking of autoaggressive lymphocytes to the pancreas. we have generated transgenic rat insulin promotor (rip)-cxcl10 mice expressing cxcl10 in the beta cells of the islets of langerhans to evaluate how bystander inflammation influences autoimmunity. ri ...	2005	16148094
virus-induced inhibition of cd1d1-mediated antigen presentation: reciprocal regulation by p38 and erk.	a critical component of the host's innate immune response involves lipid ag presentation by cd1d molecules to nk t cells. in this study we used murine cd1d1-transfected l (l-cd1) cells to study the effect of viruses on cd1d-mediated ag presentation to nkt cells and found that an infection with vesicular stomatitis and vaccinia (but not lymphocytic choriomeningitis) virus inhibited murine cd1d1-mediated ag presentation. this was under the reciprocal control of the mapks, p38 and erk, and was due ...	2005	16177070
recall proliferation potential of memory cd8+ t cells and antiviral protection.	memory cd8+ t cells play a crucial role in mediating protection from infection with viruses and other intracellular pathogens. memory t cells are not a homogenous cellular population and may be separated into central memory t cells with substantial recall proliferation capacity and effector memory t cells with limited recall proliferation capacity. it has been suggested that the protective capacity of effector memory t cells is more limited than that of central memory t cells in viral infections ...	2005	16177115
functional properties and lineage relationship of cd8+ t cell subsets identified by expression of il-7 receptor alpha and cd62l.	three major subsets of ag-experienced cd8+ t cells have been identified according to their expression of cd62l and cd127. these markers are associated with central memory t cells (cd62l+ cd127+), effector memory t cells (cd162l- cd127+), and effector t cells (cd62l- cd127-). in this study we characterized the development of these three populations during acute and chronic viral infections and after immunization with virus-like particles and determined their lineage relation and functional and pr ...	2005	16177116
innate signals compensate for the absence of pkc-{theta} during in vivo cd8(+) t cell effector and memory responses.	pkc- is central to t-helper (th) 2 cell differentiation and effector function; however, its importance for antiviral effector, and in particular memory cd8(+) t cell responses, remains unclear. we have investigated the role of pkc- during in vivo and in vitro responses against influenza virus, lymphocytic choriomeningitis virus, vaccinia virus, and replication-deficient virus-like particles. in the absence of pkc-, antiviral cd8(+) t cells presented an unresponsive phenotype in vitro, which coul ...	2005	16186501
rapid recruitment of virus-specific cd8 t cells restructures immunodominance during protective secondary responses.	in this study we investigate the attributes of virus-specific memory cd8 t cells which most effectively control secondary infections. by rechallenging mice that had cleared primary lymphocytic choriomeningitis virus infections, we revealed that the secondary response is remarkably swift. within 6 h following secondary infection, the production of gamma interferon becomes detectable directly ex vivo. during this protective phase of the secondary response, a very early elaboration of effector acti ...	2005	16188973
development of multiplex pcrs for detection of common viral pathogens and agents of congenital infections.	potential causes of congenital infection include toxoplasma gondii and viruses such as cytomegalovirus (cmv), enterovirus, hepatitis c virus, herpes simplex virus types 1 and 2 (hsv-1 and -2), human herpesvirus types 6, 7, and 8, lymphocytic choriomeningitis virus, parvovirus, rubella virus, and varicella-zoster virus. testing for each of these agents using nucleic acid tests is time consuming and the availability of clinical samples such as amniotic fluid or neonatal blood is often limited. the ...	2005	16207970
rapid production of tnf-alpha following tcr engagement of naive cd8 t cells.	the acquisition of effector functions by naive cd8 t cells following tcr engagement is thought to occur sequentially with full functionality being gained only after the initiation of division. we show that naive cd8 t cells are capable of immediate effector function following tcr engagement, which stimulates the rapid production of tnf-alpha. stimulation of splenocytes from naive mice of differing genetic backgrounds with anti-cd3epsilon mab resulted in significant production of tnf-alpha by nai ...	2005	16210607
requirement for neutralizing antibodies to control bone marrow transplantation-associated persistent viral infection and to reduce immunopathology.	bone marrow transplantation (bmt) is commonly used in the treatment of leukemia, however its therapeutic application is partly limited by the high incidence of associated opportunistic infections. we modeled this clinical situation by infecting mice that underwent bmt with lymphocytic choriomeningitis virus (lcmv) and investigated the potential of immunotherapeutic strategies to counter such infections. all mice that received bmt survived lcmv infection and developed a virus carrier status. immu ...	2005	16210661
cd8 alpha alpha homodimer expression and role in cd8 t cell memory generation during influenza virus a infection in mice.	while the precise function of cd8alphaalpha homodimer expression on peripheral t cells is uncertain, recent evidence indicates that it facilitates survival and differentiation of lymphocytic choriomeningitis virus (lcmv)-specific memory cd8alphabeta t cell precursors in vivo. here, we show that the cd8alphaalpha homodimer is also transiently up-regulated on influenza a virus-specific cd8alphabeta t cells after infection in vivo, temporally correlating with increased levels of the memory t cell d ...	2005	16231286
virus-induced polyclonal b cell activation improves protective ctl memory via retained cd27 expression on memory ctl.	different viruses elicit distinct phenotypes of memory cytotoxic t lymphocytes (ctl). this is reflected in differential expression of homing receptors and costimulatory molecules like cd27. memory ctl retained cd27 following lymphocytic choriomeningitis virus (lcmv) infection, but not after immunization with recombinant vaccinia virus or tumor cells expressing lcmv glycoprotein. stable cd27 expression on memory ctl required ligation by cd70 expressed on polyclonally activated b cells during the ...	2005	16231287
cutting edge: early ifn-gamma signaling directly enhances primary antiviral cd4+ t cell responses.	ifn-gamma drives cd4+ t cell differentiation toward the th1 phenotype (th1) and suppresses th2 development. current evidence indicates that ifn-gamma inhibits t cell proliferation and decreases t cell survival. in contrast to the above, we show here that antiviral cd4+ t cell generation after infection is reduced in the absence of ifn-gamma signals. the deficient expansion of cells was not due to perturbations in t cell sensitivity to peptide or to altered migratory patterns through nonlymphoid ...	2005	16237051
lymphocytic choriomeningitis virus.		2005	16247097
a live attenuated vaccine for lassa fever made by reassortment of lassa and mopeia viruses.	lassa virus (lasv) and mopeia virus (mopv) are closely related old world arenaviruses that can exchange genomic segments (reassort) during coinfection. clone ml29, selected from a library of mopv/lasv (mop/las) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of lasv and the rna polymerase and zinc-binding protein of mopv. replication of ml29 was attenuated in guinea pigs and nonhuman primates. in murine adoptive-transfer experiments, as little as 150 pfu of ml29 induced ...	2005	16254329
posttranslational modification of alpha-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase large is critical for virus binding.	the receptor for lymphocytic choriomeningitis virus (lcmv), the human pathogenic lassa fever virus (lfv), and clade c new world arenaviruses is alpha-dystroglycan (alpha-dg), a cell surface receptor for proteins of the extracellular matrix (ecm). specific posttranslational modification of alpha-dg by the glycosyltransferase large is critical for its function as an ecm receptor. in the present study, we show that large-dependent modification is also crucial for alpha-dg's function as a cellular r ...	2005	16254363
o mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function.	alpha-dystroglycan (alpha-dg) was identified as a common receptor for lymphocytic choriomeningitis virus (lcmv) and several other arenaviruses including the human pathogenic lassa fever virus. initial work postulated that interactions between arenavirus glycoproteins and alpha-dg are based on protein-protein interactions. we found, however, that susceptibility toward lcmv infection differed in various cell lines despite them expressing comparable levels of dg, suggesting that posttranslational m ...	2005	16254364
a role for dual viral hits in causation of subacute sclerosing panencephalitis.	subacute sclerosing panencephalitis (sspe) is a progressive fatal neurodegenerative disease associated with persistent infection of the central nervous system (cns) by measles virus (mv), biased hypermutations of the viral genome affecting primarily the matrix (m) gene with the conversion of u to c and a to g bases, high titers of antibodies to mv, and infiltration of b cells and t cells into the cns. neither the precipitating event nor biology underlying the mv infection is understood, nor is t ...	2005	16260490
reciprocal immunomodulation in a schistosome and hepatotropic virus coinfection model.	human coinfection with the helminth parasite schistosoma mansoni and hepatitis b and hepatitis c viruses is associated with increased hepatic viral burdens and severe liver pathology. in this study we developed a murine s. mansoni/lymphocytic choriomeningitis virus (lcmv) coinfection model that reproduces the enhanced viral replication and liver pathology observed in human coinfections, and used this model to explore the mechanisms involved. viral coinfection during the th2-dominated granulomato ...	2005	16272278
leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for mhc class i antigen presentation.	to detect viral infections and tumors, cd8+ t lymphocytes monitor cells for the presence of antigenic peptides bound to mhc class i molecules. the majority of mhc class i-presented peptides are generated from the cleavage of cellular and viral proteins by the ubiquitin-proteasome pathway. many of the oligopeptides produced by this process are too long to stably bind to mhc class i molecules and require further trimming for presentation. leucine aminopeptidase (lap) is an ifn-inducible cytosolic ...	2005	16272315
cutting edge: murine cd59a modulates antiviral cd4+ t cell activity in a complement-independent manner.	cd59 blocks formation of the membrane attack complex of complement by inhibiting binding of c9 to the c5b-8 complex. to investigate a role for cd59 in promoting t cell responses, we compared t cell activation in cd59a-deficient (cd59a-/-) and wild-type (wt) mice after in vitro stimulation and after infection with rvv. virus-specific cd4+ t cell responses were significantly enhanced in cd59a-/- mice compared with wt mice. similarly, cd59a-/- t cells responded more vigorously to in vitro stimulati ...	2005	16301611
reexamination of the role of ubiquitin-like modifier isg15 in the phenotype of ubp43-deficient mice.	ubp43/usp18 was described as a specific protease that removes conjugated ubiquitin-like modifier isg15 from target proteins. the severe phenotype of ubp43(-/-) mice characterized by premature death, brain cell injury, and deregulated stat1 signaling was ascribed to an enhanced conjugation of isg15. in contrast, no phenotypic changes were detected in isg15(-/-) mice. to verify the role of isg15 in the phenotype of ubp43(-/-) mice, we employed mice deficient for both isg15 and ubp43. here, we show ...	2005	16314524
molecular and cellular mechanisms, pathogenesis, and treatment of insulin-dependent diabetes obtained through study of a transgenic model of molecular mimicry.	the portrait of autoimmune diabetes mellitus or type i diabetes can be copied by a transgenic model in which either the nucleoprotein (np) or glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv) is expressed in beta cells of the islets of langerhans. in the absence of further environmental insult, diabetes does not occur. however, when lcmv or a dissimilar virus that shares cross-reactive t cell epitopes with lcmv initiates infection, diabetes ensues. if the self "viral" transgene is e ...	2005	16329191
distinct host-dependent pathogenic mechanisms leading to a similar clinical anemia after infection with lymphocytic choriomeningitis virus.	the docile strain of lymphocytic choriomeningitis virus (lcmv) induces anemia in a number of inbred strains of mice, including c3heb/fej and cba/ht animals. a difference in the kinetics of anemia and in compensatory reticulocytosis suggested that impaired erythropoiesis was the major pathogenic mechanism involved in cba/ht mice, but not in c3heb/fej mice. in both mouse strains an antierythrocyte autoantibody production that depended on the presence of functional cd4+ t lymphocytes was observed. ...	2005	16339752
novel antiviral strategies to combat human arenavirus infections.	arenaviruses merit significant attention both as tractable model systems to study acute and persistent viral infections, and as clinically important human pathogens. evidence indicates that lcmv remains present in the usa and europe and capable of causing significant morbidity in infected individuals, likely being a neglected human pathogen. moreover, new arenaviruses are being discovered in the americas on the average of one every three years, with some of them causing severe hemorrhagic fever. ...	2005	16375709
small mammal virology.	most viral infections in small mammals are transient and rarely produce clinical signs. when clinical signs do appear, they are often of a multifactorial etiology such as respiratory infection with sendai virus and the bacteria m. pulmonis in rodents. diagnosis is generally made based on clinical signs, while therapy involves treatment for concurrent bacterial infections and supportive care. small mammals may carry zoonotic viruses such as lcmv, but natural infections are uncommon. viral disease ...	2005	15585191
role of tumor necrosis factor receptors in regulating cd8 t-cell responses during acute lymphocytic choriomeningitis virus infection.	the role of tumor necrosis factor (tnf) in regulating various phases of the antiviral t-cell response is incompletely understood. additionally, despite strong evidence ascribing a role for tnf in protecting against t-cell-dependent autoimmunity, the underlying mechanisms are still obscure. to address these issues, we have investigated the role of tumor necrosis factor receptors (tnfrs) i (p55r) and ii (p75r) in regulating cd8 t-cell responses to lymphocytic choriomeningitis virus (lcmv) with wil ...	2005	15596816
expression, refolding and crystallization of murine mhc class i h-2db in complex with human beta2-microglobulin.	beta2-microglobulin (beta2m) is non-covalently linked to the major histocompatibility (mhc) class i heavy chain and interacts with cd8 and ly49 receptors. murine mhc class i can bind human beta2m (hbeta2m) and such hybrid molecules are often used in structural and functional studies. the replacement of mouse beta2m (mbeta2m) by hbeta2m has important functional consequences for mhc class i complex stability and specificity, but the structural basis for this is unknown. to investigate the impact o ...	2005	16511243
cutting edge: mhc class ii-restricted killing in vivo during viral infection.	class ii-restricted cd4 t cell-mediated killing of target cells has previously been documented in vitro but not in vivo. in this study, we demonstrate cd4-dependent mhc class ii-restricted killing in lymphocytic choriomeningitis virus-infected mice in vivo using an in vivo cytotoxicity assay that features class ii-expressing b cells as targets.	2005	15634878
t cells undergo rapid on/off but not on/off/on cycling of cytokine production in response to antigen.	inflammatory cytokines such as ifn-gamma and tnf produced by ag-stimulated cd4(+) and cd8(+) t cells are important in defense against microbial infection. however, production of these cytokines must be tightly regulated to prevent immunopathology. previous studies, conducted with balb/c mice, have suggested that 1) cd8(+) t cells maintain ifn-gamma production but transiently produce tnf in the continued presence of ag and 2) lymphocytic choriomeningitis virus-specific and in vitro-propagated eff ...	2005	15634891
arenavirus extinction through lethal mutagenesis.	viral hemorrhagic fevers represent serious human public health problems causing devastating and often lethal disease. several hemorrhagic fevers are caused by arenaviruses including lassa fever virus (lfv) and the south american viral hemorrhagic fevers (sahf). in recent years, increased air travel between africa and other areas has led to the importation of lfv into the us, europe, japan, and canada. this has raised awareness about arenaviruses as potential emerging viruses. moreover, because o ...	2005	15649566
toll-like receptor engagement converts t-cell autoreactivity into overt autoimmune disease.	autoimmune diabetes mellitus in humans is characterized by immunological destruction of pancreatic beta islet cells. we investigated the circumstances under which cd8(+) t cells specific for pancreatic beta-islet antigens induce disease in mice expressing lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) as a transgene under the control of the rat insulin promoter. in contrast to infection with lcmv, immunization with lcmv-gp derived peptide did not induce autoimmune diabetes despite l ...	2005	15654326
virus infection-associated bone marrow b cell depletion and impairment of humoral immunity to heterologous infection mediated by tnf-alpha/ltalpha.	we previously showed that influenza virus infection of mice induces a depletion of bone marrow b lineage cells due to apoptosis of early b cells mediated by a mechanism involving tnf-alpha/ltalpha. here we demonstrate that this effect is also observed with acute lymphocytic choriomeningitis virus (lcmv) infection and resulted in a deficiency of both splenic transitional b cells and mature follicular b cells. to determine whether there was an associated impairment of humoral immunity, we infected ...	2005	15657949
bone marrow is a preferred site for homeostatic proliferation of memory cd8 t cells.	proliferative renewal of memory cd8 t cells is essential for maintaining long-term immunity. in this study, we examined the contributions that various tissue microenvironments make toward the homeostatic proliferation of ag-specific memory cd8 t cells. we found that dividing memory t cells were present in both lymphoid and nonlymphoid tissues. however, the bone marrow was the preferred site for proliferation and contained a major pool of the most actively dividing memory cd8 t cells. adoptive tr ...	2005	15661882
the proline-rich homeodomain (prh/hex) protein is down-regulated in liver during infection with lymphocytic choriomeningitis virus.	the proline-rich homeodomain protein, prh/hex, participates in the early development of the brain, thyroid, and liver and in the later regenerative processes of damaged liver, vascular endothelial, and hematopoietic cells. a virulent strain of lymphocytic choriomeningitis virus (lcmv-we) that destroys hematopoietic, vascular, and liver functions also alters the transcription and subcellular localization of prh. a related virus (lcmv-arm) that does not cause disease in primates can infect cells w ...	2005	15681447
direct intralymphatic injection of peptide vaccines enhances immunogenicity.	research to enhance the efficiency of vaccines focuses mainly on improving either the adjuvant or the type and form of the antigen. this study evaluates the influence of the administration route on the efficiency of a peptide-based vaccine. peptide vaccines are generally administered subcutaneously or intradermally, from where they must reach secondary lymphatic organs to induce an immune response. we analyzed the efficacy of peptide vaccines administered directly into a lymph node. using a mhc ...	2005	15682446
rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 ifn.	in this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sdc) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (lcmv). within 24 h postinfection (pi), sdcs acquired the ability to stimulate naive lcmv-specific cd8+ t cells ex vivo. conventional (cd11chigh cd8+ and cd4+) sdc subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. the ...	2005	15699111
private specificities of cd8 t cell responses control patterns of heterologous immunity.	cd8 t cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. this cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (lcmv) and pichinde virus, where cross-reactive epitopes share six out of eight amino acids. here, however, we demonstrate more subtle and less predictable cross-reactivity between lcmv and the unrelated vaccinia virus (vv). epitope-specific t cell receptor usage differed bet ...	2005	15710651
viruses evade the immune system through type i interferon-mediated stat2-dependent, but stat1-independent, signaling.	understanding, treating, and preventing diseases caused by immunosuppression and/or persistent infections remain both a major challenge in biomedical research and an important health goal. for a virus or any infectious agent to persist, it must utilize strategies to suppress or evade the host's immune response. here, we report that two dissimilar viruses employ a common maneuver to cause a profound immunosuppression. measles virus (mv) and lymphocytic choriomeningitis virus (lcmv) interfere with ...	2005	15723812
long-term loss of canonical nkt cells following an acute virus infection.	nkt cell activation plays an important role in regulating innate and adaptive immunity during infection. we have previously found that there is a dramatic reduction in the nkt cell population on day 3 after an acute lymphocytic choriomeningitis virus (lcmv) infection. in this study, we report that this loss continued for at least 3 months and was not simply due to internalization of the tcr. concomitant with the decrease in nkt cells was an increase in the percentage of annexin v(+) nkt cells th ...	2005	15724241
myd88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection.	we investigated the roles of toll-like receptor 2 (tlr2) and myeloid differentiation factor 88 (myd88) in the course of a lymphocytic choriomeningitis virus (lcmv) infection and revealed the following: (i) studies of transfected cells and murine peritoneal macrophages demonstrated that tlr2 and myd88 are essential for the initial pro-inflammatory cytokine response (human il-8, mouse il-6) to lcmv; (ii) tlr2 knockout (ko) mice and myd88 ko mice challenged with lcmv produced less il-6 and monocyte ...	2005	15724245
inverse correlation between il-7 receptor expression and cd8 t cell exhaustion during persistent antigen stimulation.	persistence is a hallmark of infection by viruses such as hiv, hepatitis b virus, hepatitis c virus and lcmv. in the case of lcmv, persistence may often be associated with exhaustion of cd8(+) t cells. we demonstrate here that persistent antigen suppressed il-7ralpha expression and this correlated with t cell exhaustion and reduced expression of the anti-apoptotic molecule b cell leukemia/lymphoma 2 (bcl-2). in contrast, exposure to short-lived antigen only temporarily suppressed il-7ralpha expr ...	2005	15724249
cns activity of pokeweed anti-viral protein (pap) in mice infected with lymphocytic choriomeningitis virus (lcmv).	others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent pap (pokeweed antiviral protein) against a wide range of viruses. the purpose of the present study was to further elucidate the anti-viral spectrum of pap by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (lcmv).	2005	15725345
the lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral gene transfer vector to neural progenitors in the murine brain.	feline immunodeficiency virus (fiv)-based lentiviral vectors can be targeted to restricted cell types by pseudotyping with envelopes from other viruses. an fiv vector expressing bacterial beta-galactosidase (beta-gal) and pseudotyped with lymphocytic choriomeningitis virus (lcmv) envelope glycoprotein was injected into postnatal mouse brain striatum to determine neural cell-type transduction. after 3 or 7.5 weeks, the beta-gal-expressing cells included astrocytes in the striatum and in the subve ...	2005	15727934
increased epitope-specific cd8+ t cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination.	cd8+ t cells are important for clearance of neurotropic mouse hepatitis virus (mhv) strain a59, although their possible role in a59-induced demyelination is not well understood. we developed an adoptive-transfer model to more clearly elucidate the role of virus-specific cd8+ t cells during the acute and chronic phases of infection with a59 that is described as follows. c57bl/6 mice were infected with a recombinant a59 virus expressing the gp33 epitope, an h-2db-restricted cd8+ t-cell epitope enc ...	2005	15731231
complementarity in the supramolecular design of arenaviruses and retroviruses revealed by electron cryomicroscopy and image analysis.	arenaviruses are rodent-borne agents of diseases, including potentially lethal human hemorrhagic fevers. these enveloped viruses encapsidate a bisegmented ambisense single-stranded rna genome that can be packaged in variable copy number. electron cryomicroscopy and image analysis of new world pichinde and tacaribe arenaviruses and old world lymphocytic choriomeningitis virus revealed pleomorphic enveloped particles ranging in diameter from approximately 400 to approximately 2,000 a. the surface ...	2005	15731275
the cd4 molecule on cd8+ t lymphocytes directly enhances the immune response to viral and cellular antigens.	cd8+ t lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. we have previously demonstrated that costimulation of purified human cd8+ t cells induces de novo expression of the cd4 molecule and that ligation of cd4 on this cell type modulates cd8+ t cell activity in vitro. herein, we investigate how the cd4 molecule expressed on murine cd8+ t cells contributes to cd8+ cell responses in vivo by employing adoptive transfer of cd8 cells from cd4 knockout mice into ...	2005	15731353
perforin and lymphohistiocytic proliferative disorders.	perforin is critical for cytotoxicity mediated by granules present in natural killer (nk) cells and cytotoxic t lymphocytes (ctls). perforin-deficient mice have impaired cytotoxicity by nk cells and ctls, resulting in failure to control infections with certain viruses or bacteria. infection of perforin-deficient mice with lymphocytic choriomeningitis virus results in haemophagocytic lymphohistiocytosis and elevated levels of pro-inflammatory cytokines. mutations throughout the perforin gene have ...	2005	15755277
complex memory t-cell phenotypes revealed by coexpression of cd62l and ccr7.	antigen-experienced t cells have been divided into cd62l+ ccr7+ central memory (tcm) and cd62l- ccr7- effector memory (tem) cells. here, we examined coexpression of cd62l and ccr7 in lymphocytic choriomeningitis virus-specific memory cd8 t cells from both lymphoid and nonlymphoid tissues. three main points emerged: firstly, memory cells frequently expressed a mixed cd62l- ccr7+ phenotype that differed from the phenotypes of classical tem and tcm cells; secondly, tcm cells were not restricted to ...	2005	15767451
dual role of the lymphocytic choriomeningitis virus intergenic region in transcription termination and virus propagation.	each genome segment of the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv), encodes two genes in ambisense orientation, separated by an intergenic region (igr). the 3' ends of subgenomic viral mrnas have been mapped to a stem-loop structure within the igr, suggesting structure-dependent transcription termination. we have studied the role of the lcmv igr by using a minigenome (mg) rescue system based on rna analogues of the short genome segment. an ambisense mg coding for chloramp ...	2005	15767453
suppression of viral infectivity through lethal defection.	rna viruses replicate with a very high error rate and give rise to heterogeneous, highly plastic populations able to adapt very rapidly to changing environments. viral diseases are thus difficult to control because of the appearance of drug-resistant mutants, and it becomes essential to seek mechanisms able to force the extinction of the quasispecies before adaptation emerges. an alternative to the use of conventional drugs consists in increasing the replication error rate through the use of mut ...	2005	15767582
defective b cell responses in the absence of sh2d1a.	more than half of patients with x-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein sh2d1a, suffer from an extreme susceptibility to epstein-barr virus. one-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. here we show that in sh2d1a(-/-) mice, both primary and secondary responses of all ig subclasses are severely impaired in response to specific antigens. because germinal centers were a ...	2005	15774582
priming of ctls by lymphocytic choriomeningitis virus depends on dendritic cells.	appropriate activation of naive cd8(+) t cells depends on the coordinated interaction of these cells with professional apc that present antigenic peptides in the context of mhc class i molecules. it is accepted that dendritic cells (dc) are efficient in activating naive t cells and are unique in their capacity to prime cd8(+) t cell responses against exogenous cell-associated ags. nevertheless, it is unclear whether epitopes, derived from endogenously synthesized proteins and presented by mhc cl ...	2005	15778347
immune modulation of the hypothalamic-pituitary-adrenal (hpa) axis during viral infection.	compelling data has been amassed indicating that soluble factors, or cytokines, emanating from the immune system can have profound effects on the neuroendocrine system, in particular the hypothalamic- pituitary-adrenal (hpa) axis. hpa activation by cytokines (via the release of glucocorticoids), in turn, has been found to play a critical role in restraining and shaping immune responses. thus, cytokine-hpa interactions represent a fundamental consideration regarding the maintenance of homeostasis ...	2005	15802953
interferon-gamma acts directly on cd8+ t cells to increase their abundance during virus infection.	interferon-gamma (ifngamma) is important in regulating the adaptive immune response, and most current evidence suggests that it exerts a negative (proapoptotic) effect on cd8(+) t cell responses. we have developed a novel technique of dual adoptive transfer, which allowed us to precisely compare, in normal mice, the in vivo antiviral responses of two t cell populations that differ only in their expression of the ifngamma receptor. we use this technique to show that, contrary to expectations, ifn ...	2005	15809350
evaluating the immunogenicity and protective efficacy of a dna vaccine encoding lassa virus nucleoprotein.	several viruses in the arenavirus genus of the family arenaviridae cause severe, often fatal, hemorrhagic fever. one such virus, lassa virus (lv), is a frequent cause of disease in africa, and survivors often are left with substantial neurological impairment. the feasibility of protective immunization against lv infection, and the associated disease, has been demonstrated in animal models, using recombinant vaccinia viruses to deliver lassa proteins. circumstantial evidence implicates cellular i ...	2005	15823608
reduction in cd1d expression on dendritic cells and macrophages by an acute virus infection.	mice were infected with lymphocytic choriomeningitis virus (lcmv) to determine if changes in cd1d expression occurred during an acute virus infection. it is interesting that a decrease in cd1d expression on splenic dendritic cells (dc) and macrophages (mphi) was observed for at least 3 months post-lcmv infection, and vaccinia virus and vesicular stomatitis virus induced similar changes in cd1d upon infection with those viruses. the reduction of cd1d cell-surface expression on dc and mphi was ind ...	2005	15548574
suppression of viral specific primary t-cell response following intense physical exercise in young but not old mice.	intense exercise to exhaustion leads to increased susceptibility and severity of infections. t cells play an essential role in control of viral infections. whereas immune suppression is considered as a likely mechanism for exhaustive exercise-induced susceptibility to infection, we know little about viral-specific t-cell response following exhaustive exercise in young or old mice. in this study, one group of female young (10-12 wk) and old (22-24 mo) c57bl/6 mice was exposed to a single bout of ...	2005	15448122
quantification of repertoire diversity of influenza-specific epitopes with predominant public or private tcr usage.	the h-2db-restricted cd8 t cell immune response to influenza a is directed at two well-described epitopes, nucleoprotein 366 (np366) and acid polymerase 224 (pa224). the responses to the two epitopes are very different. the epitope np366-specific response is dominated by tcr clonotypes that are public (shared by most mice), whereas the epitope pa224-specific response is private (unique within each infected animal). in addition to being public, the np366-specific response is dominated by a few cl ...	2006	17082583
the role of myristoylation in the membrane association of the lassa virus matrix protein z.	the z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. both lcmv and lassa virus z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. z accumulates near the inner surface of the plasma membrane where budding takes place. furthermore, biochemical data have shown that z is strongly membrane associated. the primary sequence of z lacks a typical transmembrane domain and until now it is not unde ...	2006	17083745
virus scores a perfect 10.		2006	17088891
increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses.	the reason why severe localized or systemic virus infections enhance and aggravate bacterial superinfection is poorly understood. here we show that virus-induced ifn type i caused apoptosis in bone marrow granulocytes, drastically reduced granulocyte infiltrates at the site of bacterial superinfection, caused up to 1,000-fold higher bacterial titers in solid organs, and increased disease susceptibility. the finding that the innate antiviral immune response reduces the antibacterial granulocyte d ...	2006	17030789
acquired hydrocephalus caused by a variant lymphocytic choriomeningitis virus.		2006	17030840
resolution of a chronic viral infection after interleukin-10 receptor blockade.	a defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector t cells, which prevents viral clearance. interleukin-10 (il-10) suppresses cellular immune responses by modulating the function of t cells and antigen-presenting cells. in this paper, we report that il-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. in vivo blockade of the il-10 receptor (il-10r) with a neutralizing a ...	2006	17030951
interleukin-10 determines viral clearance or persistence in vivo.	persistent viral infections are a major health concern. one obstacle inhibiting the clearance of persistent infections is functional inactivation of antiviral t cells. although such immunosuppression occurs rapidly after infection, the mechanisms that induce the loss of t-cell activity and promote viral persistence are unknown. herein we document that persistent viral infection in mice results in a significant upregulation of interleukin (il)-10 by antigen-presenting cells, leading to impaired t ...	2006	17041596
socs-1 protects from virally-induced cd8 t cell mediated type 1 diabetes.	cd8(+) cytotoxic t lymphocytes (ctl) can rapidly kill beta-cells and therefore contribute to the development of type 1 diabetes (t1d). ctl-mediated beta-cell killing can occur via perforin-mediated lysis, fas-fas-l interaction, and the secretion of tnf-alpha or ifn-gamma. the secretion of ifn-gamma can contribute to beta-cell death directly by eliciting nitric oxide production, and indirectly by upregulating mhc class i and 'unmasking' beta-cells for recognition by ctl. earlier studies in the ri ...	2006	17045460
lcmv transmission by organ transplantation.		2006	17050901
lcmv transmission by organ transplantation.		2006	17054324
immunoproteasomes are essential for clearance of listeria monocytogenes in nonlymphoid tissues but not for induction of bacteria-specific cd8+ t cells.	microbial infections induce the replacement of constitutive proteasomes by immunoproteasomes (i-proteasomes). i-proteasomes support efficient generation of mhc class i epitopes and influence immunodominance hierarchies of cd8(+) t cells. recently, the function of i-proteasomes in antimicrobial responses was challenged by showing that the lack of i-proteasomes has no effect on induction and function of lymphocytic choriomeningitis virus-specific cd8(+) t cells. here, we show that infection with l ...	2006	17056553
the price of the cd27-cd70 costimulatory axis: you can't have it all.	t cells require costimulatory signals for optimal proliferation, differentiation, and survival and thus to induce protective immune responses. recent data, however, show that during chronic lymphocyte choriomeningitis virus (lcmv) infection, triggering of the costimulatory receptor cd27 by its ligand cd70 impedes neutralizing antibody production and leads to viral persistence. thus, while being crucial for the induction of some adaptive effector pathways, costimulation may block the development ...	2006	17060478
high prevalence of antibodies to lymphocytic choriomeningitis virus in a murine typhus endemic region in croatia.	a retrospective serological survey was carried out by the indirect immunofluorescence assay (ifa) and complement fixation (cf) test in a sample of 425 healthy residents (240 females and 185 males) to investigate whether lymphocytic choriomeningitis virus (lcmv) circulates in the rural area of the northern croatian island of vir, which is known to be endemic for murine typhus. the overall prevalence of lcmv antibodies detected by ifa was found to be 36% (155 out of 425) and 13% (54 out of 425) by ...	2006	17063527
[analysis of in vitro delivering cd8+ t epitopes by attenuated bacteria].	to analyze the efficiency of delivery for cd8(+) t cell epitopes by recombinant bacteria vectors.	2006	17077012
cutting edge: the direct action of type i ifn on cd4 t cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection.	the action of type i ifn (ifn-i) on apcs is well studied, but their direct effect on cd4 t cells is unclear. to address this, we transferred ifn-i receptor-deficient (ifn-ir(0)) and -sufficient (wild-type, wt) tcr-transgenic cd4 t cells into wt mice and analyzed their response to immunization. in response to lymphocytic choriomeningitis virus immunization, wt cd4 t cells expanded approximately 100-fold, whereas ifn-ir(0) cd4 t cells expanded <10-fold. however, both wt and ifn-ir(0) cd4 t cells e ...	2006	16517698
soluble mhc-peptide complexes containing long rigid linkers abolish ctl-mediated cytotoxicity.	soluble mhc-peptide (pmhc) complexes induce intracellular calcium mobilization, diverse phosphorylation events, and death of cd8+ ctl, given that they are at least dimeric and co-engage cd8. by testing dimeric, tetrameric, and octameric pmhc complexes containing spacers of different lengths, we show that their ability to activate ctl decreases as the distance between their subunit mhc complexes increases. remarkably, pmhc complexes containing long rigid polyproline spacers (> or =80 a) inhibit t ...	2006	16517703
taking the brake off t cells in chronic viral infection.		2006	16520769
cd69 acts downstream of interferon-alpha/beta to inhibit s1p1 and lymphocyte egress from lymphoid organs.	naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. during immune responses, the egress process can be shut down transiently. when this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. several mediators of the innate immune system are known to cause shutdown, including ...	2006	16525420