| how virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. | we developed two distinct transgenic mouse models in which virus induced insulin-dependent (type 1) diabetes mellitus (iddm). in one of these lines, the unique viral transgene was expressed in the islets of langerhans and also in the thymus, but in the other line, expression was only in the islets. insertion and expression of the viral (self) gene, per se, did not lead to iddm, (incidence < 5%). by contrast, induction of an anti-self (anti-viral) cd8+ ctl response to the same virus later in life ... | 1994 | 7889411 |
| impaired responsiveness to gamma interferon of macrophages infected with lymphocytic choriomeningitis virus clone 13: susceptibility to histoplasmosis. | lymphocytic choriomeningitis virus clone 13 (lcmv clone 13), a variant isolated from the spleens of neonatally infected mice, causes persistent infections in mice infected as adults. such persistently infected mice succumb to a normally sublethal dose of histoplasma capsulatum, and their macrophages contain overwhelming numbers of yeast cells of the fungus. both lcmv clone 13 and h. capsulatum yeast cells target and replicate in macrophages of the host. we sought to study the effects of lcmv clo ... | 1995 | 7890411 |
| cd2-deficient mice generate virus-specific cytotoxic t lymphocytes upon infection with lymphocytic choriomeningitis virus. | the major host response to many viral infections is the generation of virus-specific ctl. many protein molecules on the surfaces of both ctl and target cells interact to mediate adhesion of the cells and generate signals that lead to t cell activation and proliferation of virus-specific ctl that then mediate lysis of infected cells. one such protein, cd2, has been shown to increase the binding affinity of ctl to infected cells, and, in addition, enhance ctl activation signals. to determine wheth ... | 1993 | 7902375 |
| transfer of lymphocytic choriomeningitis disease in beta 2-microglobulin-deficient mice by cd4+ t cells. | in this study we have investigated the role of cd4+, mhc class ii-restricted cytotoxic t lymphocytes (ctls) in the disease caused by lymphocytic choriomeningitis virus (lcmv) in beta 2-microglobulin deficient (beta 2m-) mice. intracranial (i.c.) infection with lcmv resulted in death of six out of 11 beta 2m- mice. mice that survived showed a marked loss in body weight. death and loss of body weight could be prevented by immunosuppressing the mice with irradiation or cyclosporine prior to i.c. in ... | 1993 | 7903551 |
| effects of il-12 on the response and susceptibility to experimental viral infections. | effects of administered il-12 on immune responses to viral infection were evaluated. il-12-mediated effects during lymphocytic choriomeningitis virus (lcmv) infection in c57bl/6 mice were contrasted to those in either uninfected mice, or mice infected with a virus inducing a more modest t cell response, murine cytomegalovirus. mice received 0, 1, 10, 100, or 1000 ng/d of il-12 on the day prior to infection and daily on day 0 to 6 post-infection. responses were examined on day 7. low doses of il- ... | 1994 | 7905500 |
| enhanced establishment of a virus carrier state in adult cd4+ t-cell-deficient mice. | cd4+ t cells play an important role in regulating the immune response; their contribution to virus clearance is variable. mice that lack cd4+ t cells (cd4-/- mice) and are therefore unable to produce neutralizing antibodies cleared viscero-lymphotropic lymphocytic choriomeningitis virus (lcmv) strain we when infected intravenously with a low dose (2 x 10(2) pfu) because of an effective cd8+ cytotoxic t-cell (ctl) response. in contrast, infection with a high dose (2 x 10(6) pfu) of lcmv strain we ... | 1994 | 7911534 |
| enumeration of ifn-gamma producing lymphocytes by flow cytometry and correlation with quantitative measurement of ifn-gamma. | we describe a flow cytometry method to simultaneously analyze ifn-gamma production and t cell surface phenotype in freshly isolated lymphocytes without requiring prior in vitro stimulation. we show that enumeration of intracytoplasmic ifn-gamma positive t cells correlates with quantitative measurement of ifn-gamma in culture supernatant fluids. this suggests that cytokines can be reliably measured using flow cytometry. flow cytometry has the added advantage of simultaneous detection of cell surf ... | 1994 | 7913946 |
| escape of thymocytes and mature t cells from clonal deletion due to limiting tolerogen expression levels. | expression of self antigen on lymphohemopoietic cells and in the thymus has been shown to cause tolerance by negative selection. to investigate the role of self antigen expression levels on the induction of tolerance, we generated transgenic mice expressing the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) driven by the h-2kb promoter. two mouse lines differing in transgene expression levels were obtained and evaluated for the induction of tolerance to lcmv-gp. lcmv-gp high (gphi) ... | 1994 | 7923387 |
| aseptic meningitis caused by the lymphocytic choriomeningitis virus. | we present a 38-year old man suffering from a biphasic illness with fever and malaise, who developed a mild aseptic meningitis during the second phase. lymphocytic choriomeningitis virus was found to be the causative agent. | 1994 | 7924087 |
| virus-induced immunosuppression: kinetic analysis of the selection of a mutation associated with viral persistence. | infection of neonatal mice with lymphocytic choriomeningitis virus (lcmv) strain armstrong (arm) results in a lifelong persistent infection. viral variants (cytotoxic t lymphocyte [ctl] negative, persistence positive [ctl- p+]) can be isolated from the lymphoid tissues of such mice. adult mice inoculated with these ctl- p+ viruses fail to generate sufficient cytotoxic t lymphocytes to clear the acute infection and become persistently infected. by contrast, inoculation of a similar dose of the pa ... | 1994 | 7933120 |
| tissue-mediated selection of viral variants: correlation between glycoprotein mutation and growth in neuronal cells. | viral variants with different biological properties predominate in the central nervous system (cns) and lymphoid tissues of carrier mice infected at birth with the armstrong strain of lymphocytic choriomeningitis virus. the cns isolates have the same phenotype as the parental strain and cause acute infections in adult mice, while the spleen-derived isolates cause chronic infections associated with suppressed t-cell responses and susceptibility to opportunistic infections. our previous studies ha ... | 1994 | 7933132 |
| sequence heterogeneity in the termini of lymphocytic choriomeningitis virus genomic and antigenomic rnas. | sequence analysis of lymphocytic choriomeningitis virus l and s rnas has revealed evidence of heterogeneity within the termini of the genomic and antigenomic rnas. the rnas are missing from 0 to 38 bases, show characteristic patterns of deleted nucleotides at both 5' and 3' termini, and often have a nontemplated base at the terminus. the same deletions, at either the 5' or the 3' terminus of the genomic l and s rnas, are frequently found in the complementary strand of antigenomic rna, suggesting ... | 1994 | 7933159 |
| the role of cd4+ t cells in cell-mediated immunity to lcmv: studies in mhc class i and class ii deficient mice. | parameters of the virus-specific t-cell response were analysed in order to dissect the contribution of cd4+ and cd8+ t cells to cell-mediated immunity to lymphocytic choriomeningitis virus. in mhc class ii deficient mice, initial t-cell responsiveness was not impaired, but virus clearance was delayed, and virus-specific td activity declined more rapidly. furthermore, class i restricted tc memory appeared to be impaired in these mice. to directly evaluate the role of cd4+ cells in virus clearance ... | 1994 | 7939408 |
| the role of antigen in maintaining t cell memory. | evidence is summarized supporting the view that persisting antigen is key to the maintenance of immunological memory by helper and cytotoxic t cells against viruses. if these findings are generalised, they are obviously relevant to vaccine strategies. | 1994 | 7958474 |
| superantigen shock in mice with an inapparent viral infection. | subclinical lymphocytic choriomeningitis virus infection primes mice expressing a v beta 8.1d beta 2j beta 2.3c beta 2 t cell receptor as a transgene for induction of fatal hematogenous shock after administration of a dose of staphylococcal enterotoxin b (seb) that is tolerated by uninfected controls. the lethal effect is greatly diminished by prior depletion of the virus-primed cd4+ t cells. evidence of transient tumor necrosis factor (tnf) secretion is detected in serum within 1 h of seb admin ... | 1994 | 7963712 |
| establishment of the role of il-6 and tnf receptor 1 using gene knockout mice. | cytokines are known to be key players in host response to infection, immunological disorders, and tissue injury in the attempt of an organism to overcome the insult and restore homeostasis. another important aspect of cytokines, however, is their normal physiological role during development in the unchallenged organism. the most elegant way to analyze both of these functions is to introduce targeted mutations in embryonic stem cells in order to create new mouse strains deficient for a given cyto ... | 1994 | 7964164 |
| cd4+ t cells are required to sustain cd8+ cytotoxic t-cell responses during chronic viral infection. | in this study, we have examined the relative contributions of cd4+ and cd8+ t cells in controlling an acute or chronic lymphocytic choriomeningitis virus (lcmv) infection. to study acute infection, we used the lcmv armstrong strain, which is cleared by adult mice in 8 to 10 days, and to analyze chronic infection, we used a panel of lymphocyte-tropic and macrophage-tropic variants of lcmv that persist in adult mice for several months. we show that cd4+ t cells are not necessary for resolving an a ... | 1994 | 7966595 |
| lymphocytic choriomeningitis virus-induced immune dysfunction: induction of and recovery from t-cell anergy in acutely infected mice. | acute infection of immunocompetent mice by lymphocytic choriomeningitis virus induces a potent cytotoxic t-lymphocyte response that eliminates infectious virus. concurrently and paradoxically, there is a general suppression of lymphocyte responses to mitogens and to other infectious agents. splenocytes from infected mice released significant amounts of gamma interferon in response to mitogenic stimulation in vitro, but neither interleukin 2 nor interleukin 4 was similarly elevated relative to th ... | 1994 | 7966646 |
| macrophages in mice acutely infected with lymphocytic choriomeningitis virus are primed for nitric oxide synthesis. | following infection of adult mice with lymphocytic choriomeningitis virus (lcmv) there is a well documented suppression of t-cell and b-cell functions concurrent with the strong anti-lcmv immune response. macrophages have been shown to be infected and activated during acute lcmv infection and there is some evidence to indicate that there is altered antigen presentation in acutely infected mice. we have examined nitric oxide (no) production by splenic macrophages during acute infection of adult m ... | 1994 | 7968457 |
| il-2-dependent nk cell responses discovered in virus-infected beta 2-microglobulin-deficient mice. | in vivo nk cell responses to lymphocytic choriomeningitis virus were studied in cd8+ t cell-deficient mice. on day 7 after infection, dramatically elevated splenic nk cell activities were observed in both beta 2-microglobulin-negative (beta 2-m-/-) mice deficient in cd8+ t cells and anti-cd8-treated c57bl/6 animals. the enhanced responses could be attributed to increased numbers of activated nk1.1+cd3- cells. the day 7 nk cell responses in beta 2-m-/- mice, but not in normal c57bl/6 animals, wer ... | 1994 | 7989765 |
| behavioral effects of persistent lymphocytic choriomeningitis virus infection in mice. | lymphocytic choriomeningitis virus (lcmv) is a nonlytic murine virus that provides a valuable model system for studying the behavioral correlates of cns viral infection. newborn or immunosuppressed mice infected with lcmv develop a persistent tolerant infection characterized by continuous viral production. virus can be found in various body organs including lung, liver, kidney, and brain. in brain, neurons are the predominant cns cells infected and the greatest number of persistently infected ne ... | 1994 | 7993301 |
| characterization of a virus variant produced by l cells persistently infected with lymphocytic choriomeningitis virus. | continuous cultivation of murine l cells infected with lymphocytic choriomeningitis virus strain armstrong leads to production of l(arm) cells, which produce a predominantly cell-associated attenuated variant, the l(arm) virus. the relatively few infectious particles that are released have lost the ability to form plaques on l cells and to cause illness in mice even if inoculated intracerebrally. based on equal protein m(r)s, antigenicity and protein kinase activity, essentially identical result ... | 1994 | 7996136 |
| mhc class i molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice. | normally, ag is presented to cd8+ t lymphocytes as a tripartite complex consisting of peptide epitope, mhc-encoded class i heavy (alpha) chain, and beta 2-microglobulin (beta 2-m) light chain. although there is agreement about the function of both peptide and alpha-chain, the role of beta 2-m has remained uncertain. in particular, can ag be presented without its participation? we have sought to obtain an answer by using mice in which the gene for beta 2-m had been disrupted by homologous recombi ... | 1994 | 8021497 |
| non-mhc genes influence virus clearance through regulation of the antiviral t-cell response: correlation between virus clearance and tc and td activity in segregating backcross progeny. | to determine the mechanism by which non-mhc genes control the rate of virus clearance in mice infected with lymphocytic choriomeningitis virus, a segregating backcross population was studied. thirty bc1 animals were infected with virus, and virus-specific delayed-type hypersensitivity (dth) was followed by measurement of footpad swelling. ten days after virus inoculation, the animals were sacrificed and spleen virus titer together with splenic tc activity was measured. with regard to all three p ... | 1994 | 8031572 |
| antibody-mediated clearance of viruses from the mammalian central nervous system. | the novel role of antibody in clearing virus from the central nervous system without the help of other immune effectors is an important phenomenon that has only recently been documented. possible routes for antibodies across the blood-brain barrier and how they work in the cns are discussed here. | 1993 | 8044464 |
| expression of type 3 complement receptor on activated cd8+ t cells facilitates homing to inflammatory sites. | it has been reported that ag-primed t cells may express the type 3 complement receptor (cr3; cd11b/cd18, mac-1), but no clear function has been ascribed to this molecule on t cells. in our study, we have used a nondepleting mab to cr3 (5c6) to study the relevance of cr3 expression for t-cell extravasation at inflammatory foci. the in vivo administration of 5c6 significantly reduced the severity of the t cell-mediated meningitis induced by intracerebral inoculation of lymphocytic choriomeningitis ... | 1994 | 8051407 |
| reduced thymic maturation but normal effector function of cd8+ t cells in cd8 beta gene-targeted mice. | cd8 is a cell surface glycoprotein on major histocompatibility complex class i-restricted t cells. thymocytes and most peripheral t cells express cd8 as heterodimers of cd8 alpha and cd8 beta. the intestinal intraepithelial lymphocytes (iel), which have been suggested to be generated extrathymically, express cd8 predominantly as homodimers of cd8 alpha. we have generated cd8 beta gene-targeted mice. cd8 alpha+ t cell population in the thymus and in most peripheral lymphoid organs was reduced to ... | 1994 | 8064243 |
| association of ld-restricted peptides with the wild-derived mouse lw16 mhc class i molecule. | previous serological analysis of untreated splenocytes and l cell transfectants expressing the wild-derived mouse major histocompatibility complex (mhc) class i molecule, lw16, demonstrated the presence of two forms of this molecule in the cell lysates, one reactive with both the alpha 2 domain-reactive monoclonal antibody (mab) 30-5-7 and the alpha 3 domain-reactive mab 28-14-8 (30-5-7+ 28-14-8+), and the other reactive with only the latter of the two (30-5-7- 28-14-8+). furthermore, the analys ... | 1994 | 8065377 |
| cd8+ t lymphocyte-mediated antiviral immunity in mice as a result of injection of recombinant viral proteins. | a major portion of the nucleoprotein (amino acids 67 through 300) and the glycoprotein-2 of lymphocytic choriomeningitis (lcm) virus were synthesized by using recombinant technology and were injected together with sds twice in portions of 5 micrograms into balb/c mice. as evidenced by diminished replication of lcm challenge virus, both proteins induced antiviral immunity, which was comparable in extent with the immunity caused by infection with lcm vaccinia recombinant viruses. primed lcm-viral ... | 1994 | 8077665 |
| induction of protective cytotoxic t cells with viral proteins. | induction of cd8+, class i-restricted t cells by non-infectious, exogenous antigens has been documented for model protein antigens such as ovalbumin and for major histocompatibility complex restricted short peptides in viral and tumor systems. however, the protective capacity of cytotoxic t cells induced by conventional proteins has not been tested in vivo so far. we, therefore, evaluated the induction of protective cytotoxic t cells against three different full-length recombinant viral proteins ... | 1994 | 8088338 |
| antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking cd8+ t lymphocytes because of disruption of the beta 2-microglobulin gene. | mice infected intracerebrally with lymphocytic choriomeningitis virus (lcm virus) develop a characteristic central nervous system disease and usually die. if the intravenous or intraperitoneal route is used, the infection leads to less severe clinical signs and the virus is eliminated. illness and virus clearance are immunological phenomena, which are assumed to be caused exclusively by cd8+ t lymphocytes. in contrast, of the two phases of a delayed-type hypersensitivity reaction caused by inocu ... | 1993 | 8093219 |
| high frequency of cross-reactive cytotoxic t lymphocytes elicited during the virus-induced polyclonal cytotoxic t lymphocyte response. | polyclonal stimulation of cd8+ cytotoxic t lymphocytes (ctl) occurs during infection with many viruses including those not known to transform ctl or encode superantigens. this polyclonal ctl response includes the generation of high levels of allospecific ctl directed against many class i haplotypes. in this report we investigated whether the allospecific ctl generated during an acute lymphocytic choriomeningitis virus (lcmv) infection of c57bl/6 mice were stimulated specifically by antigen recog ... | 1993 | 8093891 |
| tolerance induction by clonal deletion of cd4+8+ thymocytes in vitro does not require dedicated antigen-presenting cells. | the cellular requirements of t cell tolerance induction in the thymus by clonal deletion was investigated by using an in vitro assay: thymocytes from mice expressing a transgenic tcr specific for lymphocytic choriomeningitis virus (lcmv) and h-2db were co-cultured with various h-2b cell types as antigen-presenting cells in the presence of the antigenic lcmv peptide. the results revealed that all cell lines examined including embryonic and transformed fibroblasts, melanoma cells, cortical thymic ... | 1993 | 8095457 |
| autoimmune diabetes can be induced in transgenic major histocompatibility complex class ii-deficient mice. | insulin-dependent diabetes mellitus (iddm) is an autoimmune disease marked by hyperglycemia and mononuclear cell infiltration of insulin-producing beta islet cells. predisposition to iddm in humans has been linked to the class ii major histocompatibility complex (mhc), and islet cells often become aberrantly class ii positive during the course of the disease. we have used two recently described transgenic lines to investigate the role of class ii molecules and cd4+ t cells in the onset of autoim ... | 1993 | 8101862 |
| lymphocytic choriomeningitis virus induces a chronic wasting disease in mice lacking class i major histocompatibility complex glycoproteins. | lymphocytic choriomeningitis virus (lcmv) induces a chronic, wasting syndrome when injected intracerebrally into h-2b mice homozygous for a beta 2-microglobulin (beta 2-m (-/-)) gene disruption. these mice have very few cd8+ t cells and express little class i mhc glycoprotein, though minimal levels of the h-2db molecule have been detected on in vitro cultured beta 2-m (-/-) cells. the underlying immunopathological process in these beta 2-m (-/-) mice is mediated by virus immune cd4+ effectors. h ... | 1993 | 8103060 |
| resistance of lymphocytic choriomeningitis virus to alpha/beta interferon and to gamma interferon. | the susceptibility to alpha/beta interferon (ifn-alpha/beta) or to gamma interferon (ifn-gamma) of various lymphocytic choriomeningitis virus (lcmv) strains was evaluated in c57bl/6 mice and in various cell lines. anti-ifn-gamma treatment in vivo revealed that the lcmv strains armstrong, aggressive, and we were most susceptible to ifn-gamma whereas traub, cl 13-armstrong, and docile were resistant. the same pattern of susceptibility to recombinant ifn-gamma was observed in vitro. in vivo treatme ... | 1994 | 8107255 |
| evidence for a differential avidity model of t cell selection in the thymus. | positive and negative selection of a lymphocytic choriomeningitis virus (lcmv) peptide-specific, h-2db-restricted t cell clone (p14) was studied using tap1- and tap1+ mice transgenic for p14 t cell receptor (tcr) alpha and beta genes. positive selection of transgenic cd8+ p14 cells was impaired in tap1- mice. addition of the lcmv peptide to tap1- fetal thymic organ cultures (ftocs) at low and high concentrations induced positive and negative selection of cd8+ p14 cells, respectively, while addit ... | 1994 | 8124708 |
| positive and negative thymocyte selection induced by different concentrations of a single peptide. | t lymphocyte maturation is dependent on interactions between the t cell receptor (tcr) expressed on the developing thymocyte and intrathymic major histocompatibility complex (mhc)-peptide ligands. the relation between the peptide-mhc complex that results in negative or positive selection has not been identified. here, the requirements for the maturation of thymocytes expressing a defined transgenic tcr specific for a viral peptide are studied in fetal thymic organ culture. low concentrations of ... | 1994 | 8128249 |
| separation of thymic education from antigen presenting functions of major histocompatibility complex class i molecules. | participation of transmembrane (tm) and glycosyl-phosphatidylinositol (gpi) anchored h-2db molecules in antigen presentation and thymic selection events was investigated using transgenic mice. both gpi-db and tm-db can efficiently present h-y antigen, influenza and lymphocytic choriomeningitis virus (lcmv) peptides to primed cytotoxic, h-2db-restricted t cells. transgenic mice expressing gpi-db, although unable to reject tm-db skin grafts, nevertheless generate secondary ctl responses which can ... | 1994 | 8132209 |
| pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. | il-10 inhibits macrophage-dependent antigen presentation, cytokine production, and generation of allospecific cells in vitro. these findings have lead to the widespread expectation that il-10 may be a useful immunosuppressive agent to inhibit allograft rejection or autoimmunity in vivo. we used two experimental paradigms to study effects of murine il-10 on in vivo immune responses. first, fetal pancreata or adult pancreatic islets from transgenic mice expressing il-10 in pancreatic beta cells (i ... | 1994 | 8132775 |
| immune exhaustion: driving virus-specific cd8+ t cells to death. | | 1993 | 8137116 |
| murine hepatitis caused by lymphocytic choriomeningitis virus. i. the hepatic lesions. | the hepatitis that occurs after adult mice are infected with lymphocytic choriomeningitis (lcm) virus is immune mediated, although the details of the pathogenetic mechanisms are largely unknown. to better understand the sequence of events leading to alterations typical for hepatitides with immunopathogenesis, livers of immunocompetent mice infected with lcm virus were examined. | 1994 | 8139267 |
| analysis of neutralizing antibody specificities of different strains of lymphocytic choriomeningitis virus with strain-specific immune sera. | the present study was aimed at comparing specificities and cross-reactivities of immune mouse sera obtained from mice infected with a low (2 x 10(2) or 20 immunological infectious focus units (ifu) or high (2 x 10(6) ifu) dose of various strains of lymphocytic choriomeningitis virus (lcmv). neutralization titres of the various antisera were determined by an infectious focus reduction assay. this assay was performed on mc57g and on vero e6 cells using the commonly utilized laboratory strains of l ... | 1993 | 8140290 |
| prevalence of lymphocytic choriomeningitis virus infection in a human population of argentina. | the activity of lymphocytic choriomeningitis virus (lcmv) in the endemic area of argentine hemorrhagic fever has been previously reported and represents the first evidence of the coexistence of two arenaviruses pathogenic for humans, junin and lcmv, in the same geographic area. data are presented on the prevalence of lcmv human infection in a 10,000-km2 area located in santa fe province, argentina. study subjects were males, 15-65 years old, living and/or working in the rural area of 41 localiti ... | 1994 | 8147496 |
| cytotoxicity mediated by t cells and natural killer cells is greatly impaired in perforin-deficient mice. | perforin-deficient mice have been generated by homologous recombination to determine whether the effects of cd8+ cytolytic t cells and natural killer cells are mediated by pore formation involving perforin. these mice are viable and fertile and have normal numbers of cd8+ t cells and natural killer cells which do not lyse virus-infected or allogeneic fibroblasts or natural killer target cells in vitro. the mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumo ... | 1994 | 8164737 |
| mhc class i and non-mhc-linked capacity for generating an anti-viral ctl response determines susceptibility to ctl exhaustion and establishment of virus persistence in mice. | the influence of the murine mhc gene complex h-2 class i alleles or of the genetic background and the role of virus variants on establishment of a persistent infection with lymphocytic choriomeningitis virus (lcmv) was analyzed in immunocompetent mice of h-2d haplotype by evaluation of cytotoxic t cell responses. susceptibility to establishment of a virus carrier state increased in various h-2d mice with lower ctl response and slower ctl kinetics. low responder balb/c-h-2dm2, lacking h-2ld molec ... | 1994 | 8176216 |
| limiting the available t cell receptor repertoire modifies acute lymphocytic choriomeningitis virus-induced immunopathology. | the invariably fatal immunopathological disease that follows intracerebral injection of cba/ca (h-2k) mice with 1000 pfu of lymphocytic choriomeningitis virus (lcmv) generally fails to develop in congenic mice transgenic for a v beta 8.1d beta 2j beta 2.3c beta 2 t cell receptor (tcr) gene. the majority of these lcmv-infected tcr-transgenic mice show a substantial meningitis of delayed onset, that resolves without causing any obvious clinical impairment. this inflammatory process depends on the ... | 1994 | 8182114 |
| antigen presentation and cytotoxic t lymphocyte killing studied in individual, living cells. | interactions between individual, living fibroblasts and cytotoxic t lymphocyte (ctl) clones were analyzed by using video-enhanced differential interference contrast and fluorescence microscopy in a multimode configuration. fibroblasts expressing known major histocompatibility complex i alleles (mc57: h-2b; balb: h-2d) were sensitized for killing by incubating or microinjecting them with peptide fragments of lymphocytic choriomeningitis virus. previous determination of the ctl clones' specificity ... | 1994 | 8184542 |
| cross-reactivities in memory cytotoxic t lymphocyte recognition of heterologous viruses. | analyses of the relationships between different viruses and viral proteins have focused on homologies between linear amino acid sequences, but cross-reactivities at the level of t cell recognition may not be dependent on a conserved linear sequence of several amino acids. the ctl response to pichinde virus (pv) and vaccinia virus (vv) in c57bl/6 mice previously immunized with lymphocytic choriomeningitis virus (lcmv) included the reactivation of memory cytotoxic t lymphocyte (ctl) specific to lc ... | 1994 | 8195718 |
| a transgenic mouse model to assess the interaction of cytotoxic t lymphocytes with virally infected, class i mhc-expressing astrocytes. | astrocytes provide crucial support for neurons and their impairment by viruses or their interactions with anti-viral or autoimmune responses could contribute to neurological disease. we have developed a transgenic mouse model to assess lymphocyte-astrocyte interactions. the major histocompatibility complex (mhc) class i molecule, db, was expressed in astrocytes under the transcriptional control of regulatory sequences from the glial fibrillary acidic protein (gfap) gene. baseline cerebral mhc cl ... | 1994 | 8207120 |
| altered tissue distribution of viral replication and t cell spreading is pivotal in the protection against fatal lymphocytic choriomeningitis in mice after neutralization of ifn-alpha/beta. | ifn-alpha/beta have been shown to play a central role in the development of lymphocytic choriomeningitis and increasing attention has been focused on this group of cytokines as early regulatory factors directing t lymphocyte responses. in the present study, injection of antiserum to ifn-alpha/beta prevented the development of lymphocytic choriomeningitis, was associated with the absence of detectable expression of early 2'-5' oligo-adenylate synthetase mrna and coincided with viremia of lymphocy ... | 1994 | 8207238 |
| cytotoxic t lymphocytes cleanse viral gene products from individually infected neurons and lymphocytes in mice persistently infected with lymphocytic choriomeningitis virus. | lymphocytes and/or monocytes/macrophages carry viral genetic information in most, if not all, persistent and latent viral infections, and serve as potential reservoirs for maintaining or reintroducing the infection. similarly, neurons can be persistently infected by several dna and rna viruses whose continued presence can alter the physiologic function of these cells, leading to disorders in neurotransmitters and disease. here, we document that adoptive transfer of virus-specific cytotoxic t lym ... | 1993 | 8212586 |
| the lack of cd8 alpha cytoplasmic domain resulted in a dramatic decrease in efficiency in thymic maturation but only a moderate reduction in cytotoxic function of cd8+ t lymphocytes. | the glycoprotein cd8 is believed to play an important role in the maturation and function of mhc class i-restricted t lymphocytes. cd8 has been proposed to function as a co-receptor of the tcr to participate in signal transduction, possibly through its cytoplasmic domain that binds to protein tyrosine kinase p56lck. a t cell-specific transgene encoding cd8 alpha truncated at the cytoplasmic domain ("tailless cd8 alpha"), was introduced into cd8 alpha-deficient mice. this animal model was used to ... | 1993 | 8223860 |
| effector t-cell induction and t-cell memory versus peripheral deletion of t cells. | | 1993 | 8225368 |
| replication of lymphocytic choriomeningitis virus is restricted in terminally differentiated neurons. | we have investigated the replication of lymphocytic choriomeningitis virus (lcmv) before and after the nerve growth factor (ngf)-induced transdifferentiation of pc12 cells from the chromaffin to the neuron-like phenotype. untreated and ngf-treated cells were equally susceptible to lcmv infection; however, the viral yield was found to be 1,000-fold lower in ngf-differentiated pc12 cells. the reduced viral yield correlated with restricted lcmv replication and transcription within the infected cell ... | 1993 | 8230458 |
| contamination of transplantable tumors, cell lines, and monoclonal antibodies with rodent viruses. | different biological materials were tested for murine viral contamination by using the mouse/rat antibody production test. of 297 tumors examined, 75 (25.3%) were contaminated. considerable differences in the contamination rate became evident when transplantable tumors from in vitro and from in vivo passages were compared. of 186 tumors that had been propagated in animals, 36.6% were positive, whereas only 7 of 111 (6.3%) tumors propagated in vitro were contaminated. the highest rate of contamin ... | 1993 | 8231085 |
| immune responses in interleukin-2-deficient mice. | the role of costimulatory signals in t cell induction was evaluated in mice lacking the interleukin-2 (il-2) gene. in vitro secondary antiviral t cell responses were absent unless il-2 was added, confirming the crucial role of il-2 in vitro. in vivo, primary and secondary cytotoxic t cell responses against vaccinia and lymphocytic choriomeningitis virus were within normal ranges. b cell reactivity to vesicular stomatitis virus was not impaired. t helper cell responses were delayed but biological ... | 1993 | 8235625 |
| rous-whipple award lecture. viruses and diseases of the twenty-first century. | | 1993 | 8238240 |
| teratogenic effects of neonatal arenavirus infection on the developing rat cerebellum are abrogated by passive immunotherapy. | the effects of viral infection on the developing nervous system and the potential of passive immunotherapy to protect against infection were examined. when 4-day-old lewis rats were injected intracerebrally with lymphocytic choriomeningitis virus (lcmv) the majority of stem cells within the external granular layer of the developing cerebellum became infected. the infection progressed to the molecular layer, internal granular layer, and the purkinje cells. by 15 days postinfection the molecular a ... | 1993 | 8249289 |
| vaccination with two different vaccinia recombinant viruses: long-term inhibition of secondary vaccination. | the effects of immunity to vaccinia virus on the efficiency of vaccination with a vaccinia recombinant virus were studied. in mice the efficiency and duration of the b-cell response to the recombinant gene product of a second vaccinia recombinant virus were suppressed for more than 9 months, i.e. practically lifelong. antibody titres against the recombinant gene product were not only lower but also lasted for a shorter time. thus, immunity to vaccinia virus may influence both the titre and durat ... | 1993 | 8249436 |
| enhancement of disease by neutralizing antiviral antibodies in the absence of primed antiviral cytotoxic t cells. | the effects of neutralizing antibodies on the disease course in mice infected with the noncytopathic lymphocytic choriomeningitis virus (lcmv) were evaluated. whereas non-neutralizing antisera exhibiting high enzyme-linked immunosorbent assay titers had no effect on t cell responses and their consequences, neutralizing antisera modulated them variably. neutralizing antibodies were able to prevent lethal choriomeningitis after intracerebral infection with a neurotropic lcmv-isolate (armstrong) al ... | 1993 | 8258339 |
| peripheral clonal deletion of antiviral memory cd8+ t cells. | antiviral cytotoxic memory cd8+ t cells adoptively transferred to mice which are persistently infected with lymphocytic choriomeningitis virus we or docile initially proliferated extensively; they either caused the death of the recipient or, alternatively, disappeared within a few days. apparently, the complete and coordinated induction and stimulation by widely distributed viral antigen caused these memory t cells to die before virus had been eliminated from the host. thus memory t cells are as ... | 1993 | 8258345 |
| mechanism of lymphocytic choriomeningitis virus entry into cells. | the path that the arenavirus lymphocytic choriomeningitis virus (lcmv) uses to enter rodent fibroblastic cell lines was dissected by infectivity and inhibition studies and immunoelectron microscopy. lysosomotropic weak bases (chloroquine and ammonium chloride) and carboxylic ionophores (monensin and nigericin) inhibited virus entry, assessed as virus nucleoprotein expression at early times post-infection, indicating that the entry process involved a ph-dependent fusion step in intracellular vesi ... | 1994 | 8259643 |
| congenital lymphocytic choriomeningitis virus infection in twins. | | 1993 | 8265286 |
| cerebral expression of multiple cytokine genes in mice with lymphocytic choriomeningitis. | the simultaneous expression of multiple cytokine genes was examined within the brain and peripheral organs of euthymic and congenic athymic mice during the course of lymphocytic choriomeningitis (lcm) induced by the intracranial inoculation of lcm virus. in euthymic mice, levels of tnf-alpha, il-1 alpha, il-6, and il-1 beta mrna in the brain increased early in infection and further increased with the progression of disease; the level of ifn-gamma mrna was expressed at high levels late in infecti ... | 1994 | 8283046 |
| peptide-induced t-cell tolerance to prevent autoimmune diabetes in a transgenic mouse model. | a synthetic peptide corresponding to an immunodominant epitope of lymphocytic choriomeningitis virus glycoprotein (lcmv gp) was used to prime or to tolerize cd8+ t cells in vivo, dependent on mode of immunization. peptide-specific tolerance was then examined in transgenic mice expressing lcmv gp in the beta islet cells of the pancreas; these mice develop cd8+ t-cell-mediated diabetes within 8-14 days after lcmv infection. specific peptide-induced tolerance prevented autoimmune destruction of bet ... | 1994 | 8290546 |
| acidic ph triggers lcmv membrane fusion activity and conformational change in the glycoprotein spike. | membrane fusion activity of the glycoprotein (gp) complex of lcmv was determined using the r18 fluorescent dequenching assay. utilization of an endosomal entry route by lcmv and acidic activation of the membrane fusion activity were indicated by the inhibition of lcmv infection at an early stage by the lysosomal weak base chloroquine and the ionophore monensin. when lcmv was mixed with r18-labeled liposomes with a lipid composition mimicking that of the endosome, dequenching occurred only at aci ... | 1994 | 8291229 |
| high frequency of t lymphocytes committed to interferon-gamma transcription upon polyclonal activation in spleen from lymphocytic choriomeningitis virus-infected mice. | splenic t lymphocytes from c3h/heour mice infected for 7 days with lymphocytic choriomeningitis virus (lcmv) do not proliferate in response to concanavalin a (con a). although the il-2 gene remained silent after polyclonal activation, the gene encoding the p55 chain of the il-2 receptor was normally transcribed. these data indicated that the co-ordinated expression of the unique wave of cytokine and cytokine receptor expression, associated with t cell triggering, did not occur in t lymphocytes f ... | 1993 | 8318449 |
| lysis of infected cells in vivo by antiviral cytolytic t cells demonstrated by release of cell internal viral proteins. | immunocompetent adult mice infected with lymphocytic choriomeningitis virus (lcmv) generate a strong antiviral cytotoxic t cell response that clears virus from all organs. although there is good evidence that immune cytotoxic t lymphocytes (ctl) kill target cells in vitro, in vivo it is debated whether antiviral activity of cd8+ t cells is mediated via direct target cell lysis or via soluble mediators. to demonstrate cd8+ t cell-mediated destruction of infected cells in vivo a specific cell-inte ... | 1993 | 8325330 |
| normal b lymphocyte development but impaired t cell maturation in cd45-exon6 protein tyrosine phosphatase-deficient mice. | the transmembrane tyrosine phosphatase cd45 is expressed in multiple isoforms on all nucleated hematopoietic cells, resulting from alternative splicing of variable exons. we generated mice with a mutation in the variable cd45 exon 6, using homologous recombination. in mice homozygous for the cd45-exon6 mutation, b cells and most t cells did not express cd45. development of b cells appeared normal, although ig mu-induced proliferation was completely abrogated. thymocyte maturation was blocked at ... | 1993 | 8334701 |
| t cell immunity after a viral infection versus t cell tolerance induced by soluble viral peptides. | the fate of in vivo activated cd8+ cytotoxic t cells was studied in transgenic mice expressing a t cell receptor (tcr) specific for the lymphocytic choriomeningitis virus (lcmv) glycoprotein peptide 33-41 presented by major histocompatibility complex (mhc) class i molecules. lcmv infection of tcr transgenic mice induced lcmv-specific effector and memory t cells whereas injection of soluble lcmv glycoprotein peptide 33-41 resulted in tolerance by peripheral deletion and anergy of lcmv-specific t ... | 1993 | 8344359 |
| lipopolysaccharide inhibits the production of lymphocytic choriomeningitis virus in a human monocytic cell line. | the human monocytic cell line thp-1 was used as a model to study the mechanism of infection in the monocyte/macrophage, a natural target of lymphocytic choriomeningitis virus (lcmv) infection in vivo. both the virulent strain, lcmv.we, and the avirulent strain, lcmv.arm, infected thp-1 cells, but did not stimulate thp-1 cells to secrete interleukin 1 (il-1) or tumour necrosis factor (tnf-alpha). when lipopolysaccharide (lps) was added to thp-1 cells together with lcmv, an 80 to 90% reduction in ... | 1993 | 8345356 |
| hydrocephalus complicating lymphocytic choriomeningitis virus infection. | | 1993 | 8345985 |
| t-cell responsiveness to lcmv segregates as a single locus in crosses between balb/ca and c.b-17 mice. evidence for regulation by a gene outside the igh region. | the course of systemic infection with lymphocytic choriomeningitis virus (lcmv) was studied in balb/ca and c.b-17 mouse strains differing in the immunoglobulin heavy chain region (igh). susceptibility to intracerebral infection and the ability to clear the virus differed significantly between these presumably congenic strains, suggesting that a gene in the igh region might influence the course of this infection. a difference in virus spread prior to appearance of the immune response could not ex ... | 1993 | 8356397 |
| trafficking of activated cytotoxic t lymphocytes into the central nervous system: use of a transgenic model. | we have used cell or tissue-specific promoters to express lymphocytic choriomeningitis virus (lcmv) proteins in selected cells in independent lines of transgenic mice. upon adoptive transfers into these mice, mhc-restricted lcmv-specific cytotoxic t lymphocytes homed specifically to either the choroid plexus (sv40 promoter) or beta cells of the islets of langerhans (rat insulin promoter). the availability of promoters specific for neurons, oligodendrocytes and astrocytes makes this approach comp ... | 1993 | 8360331 |
| programmed cell death of t lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency. | acute viral infections induce immune deficiencies, as shown by unresponsiveness to mitogens and unrelated antigens. t lymphocytes isolated from mice acutely infected with lymphocytic choriomeningitis virus (lcmv) were found in this study to undergo activation-induced apoptosis upon signalling through the t-cell receptor (tcr)-cd3 complex. kinetic studies demonstrated that this sensitivity to apoptosis directly correlated with the induction of immune deficiency, as measured by impaired proliferat ... | 1993 | 8371341 |
| a simple nucleic acid amplification assay for the rapid detection of junín virus in whole blood samples. | argentine hemorrhagic fever (ahf) is an endemoepidemic disease with cardiovascular, renal and neurologic alterations acquired in the richest farming land in argentina. it is caused by junín virus, one of the few human pathogenic arenaviruses. the s rna of junín virus has been molecularly cloned and its nucleotide sequence determined in our laboratory. this information was used to develop a rapid nucleic acid-based diagnostic test commensurate with the low viraemia detected in ahf patients. junín ... | 1993 | 8383393 |
| alloreactive cytotoxic t lymphocytes generated in the presence of viral-derived peptides show exquisite peptide and mhc specificity. | the nature of alloreactivity to mhc molecules has been enigmatic, primarily because of the observation that allogeneic responses are considerably stronger than syngeneic responses. to better determine the specificity potential of allogeneic responses, we have generated alloreactive ctl specific for exogenous, viral-derived peptide ligands. this approach allowed us to critically evaluate both the peptide- and mhc-specificity of these alloreactive t cells. exploiting the accessibility of the h-2ld ... | 1993 | 8392095 |
| b cells induce apoptosis via a novel mechanism in fibroblasts infected with mouse hepatitis virus. | b cells from nonimmune mice mediate the cytolysis of fibroblasts infected with the coronavirus, mouse hepatitis virus (mhv), strain a59. in this investigation, we report that splenic b cells and a b cell hybridoma induced the fragmentation of mhv-infected target cell dna into a nucleosomal ladder pattern, characteristic of apoptosis. to determine the mechanism by which b cells mediated this killing event, we used criteria previously established for the killing of target cells by cytotoxic t lymp ... | 1993 | 8392406 |
| peripheral t cells in mice lacking p56lck do not express significant antiviral effector functions. | mutant mice lacking p56lck, the t cell-specific protein tyrosine kinase, have a profound thymic atrophy and possess only an immature thymocyte population. only 5 to 10% of normal levels of mature t cells (tcr-alpha beta+, cd4+, or cd8+) are present in these mice. these t cells, but also b cells of mutant mice, can be activated by mitogens, and t cells proliferate upon stimulation with il-2 or mab against the tcr. thus, it appears that selected t cells can mature without lck and that they may hav ... | 1993 | 8393038 |
| virus-induced immunosuppression. 1. age at infection relates to a selective or generalized defect. | viruses that persist must develop strategies to escape immunologic surveillance in order to survive. investigation of lymphocytic choriomeningitis virus (lcmv)-induced persistence has indicated that this virus avoids immune clearance mainly by aborting the viral specific cytotoxic t lymphocyte (ctl) response, a response that is necessary for terminating viral infection. this study demonstrates that persistence established in immunologically immature newborns selectively depletes the lcmv-specifi ... | 1993 | 8393233 |
| targeted disruption of irf-1 or irf-2 results in abnormal type i ifn gene induction and aberrant lymphocyte development. | interferon regulatory factor 1 (irf-1), a transcriptional activator, and its antagonistic repressor, irf-2, were originally identified as regulators of the type i interferon (ifn) system. we have generated mice deficient in either irf-1 or irf-2 by gene targeting in embryonic stem cells. irf-1-deficient fibroblasts lacked the normally observed type i ifn induction by poly(i):poly(c), while they induced type i ifn to similar levels as the wild type following newcastle disease virus (ndv) infectio ... | 1993 | 8402903 |
| comparison of the sensitivity of in vivo and in vitro assays for detection of antiviral cytotoxic t cell activity. | sensitivities of in vitro and in vivo assays for the detection of lymphocytic choriomeningitis virus (lcmv)-specific ctl were compared. measurement of primary cytotoxicity was the least sensitive of all the tested assays. however, when the same 51cr release assays were performed after in vitro restimulation, this in vitro method was found to be more sensitive than all of the five in vivo assays tested. assessment of ctl-mediated protection against lcmv replication in spleens was most sensitive a ... | 1993 | 8402949 |
| mechanism and consequence of viral persistence in cells of the immune system and neurons. | viral persistence depends on a virus having a non-lytic strategy of replication and the ability to escape immune surveillance. cells of the immune system (lymphocytes/monocytes/macrophages) and central nervous system (neurons) are most often infected by dna and rna viruses that persist. cytotoxic t lymphocytes (ctl) are the primary host defense that aborts or prevents viral persistence. viral interaction with these specialized cells and of such infected cells with ctl is explored in this paper. | 1993 | 8407238 |
| transforming growth factor-beta expression and natural killer cell responses during virus infection of normal, nude, and scid mice. | the experiments presented here assess the contribution of t cells to nk cell regulation and transforming growth factor-beta (tgf-beta) production. the kinetics of nk cell activation in the absence of t cells was evaluated by comparing responses in athymic nude and scid mice to those in normal c3h/hen, c57bl/6, and balb/c mice during lymphocytic choriomeningitis virus (lcmv) infection. t cell-deficient mice exhibited high nk cell activity for longer periods of time post-infection. to determine wh ... | 1993 | 8409446 |
| cd8 is needed for positive selection but differentially required for negative selection of t cells during thymic ontogeny. | during thymic development, immature thymocytes expressing major histocompatibility complex (mhc) class i-restricted t cell receptors (tcr) differentiate into cd8+ t cells with cytolytic functions. to evaluate the role of cd8 in positive and negative selection during thymic ontogeny, mice rendered cd8-null by gene targeting were bred with three lines of transgenic mice expressing unique mhc class i-restricted tcr. in all three instances cd8 was required for positive selection of mhc class i-restr ... | 1993 | 8419174 |
| an anti-lymphocytic choriomeningitis virus ribozyme expressed in tissue culture cells diminishes viral rna levels and leads to a reduction in infectious virus yield. | ribozymes, rna molecules which cleave rna in a sequence-specific manner, are a promising tool in the development of specific antiviral therapies. the viruses most susceptible to ribozymes may be those in which all aspects of the viral life cycle depend on rna, with no dna intermediate. consequently, we have chosen as a model one such virus, the arenavirus lymphocytic choriomeningitis virus (lcmv), and have previously reported the design of specific anti-lcmv ribozymes (z. xing and j. l. whitton, ... | 1993 | 8445712 |
| t cell-dependent ifn-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs. | the antiviral relevance of soluble mediators that may operate in the vicinity of virus specific effector t cells was investigated. mice were immunized with vesicular stomatitis virus (vsv) wild type (wt) and subsequently challenged with a mixture of two vaccinia recombinant viruses, one expressing the nucleoprotein of vsv (vacc-vsv-np) the other expressing the glycoprotein of lymphocytic choriomeningitis virus (vacc-lcmv-gp). it was determined whether or not the vsv wt-induced memory t cell resp ... | 1993 | 8450214 |
| a common-source outbreak of callitrichid hepatitis in captive tamarins and marmosets. | callitrichid hepatitis (ch) is a highly fatal, emerging arenavirus disease of captive south american marmosets and tamarins (callitrichidae), including the endangered golden lion tamarin. a common-source outbreak of ch in golden lion tamarins and pygmy marmosets at a us zoo resulted from a single feeding of the primates with newborn mice in apparently infected with lymphocytic choriomeningitis virus (lcmv). isolates from livers of mice and primates were related to isolates from previous ch outbr ... | 1993 | 8450260 |
| enhanced positive selection of a transgenic tcr by a restriction element that does not permit negative selection. | very little is known about the conformational properties of the mhc molecules that are able to signal positive selection of a given tcr. to try to understand these parameters and to determine whether these requirements are shared with interactions during negative selection and antigen recognition, we have studied selection and antigen recognition of a transgenic tcr (specific for lymphocytic choriomeningitis virus glycoprotein and h-2db) in the context of two db mutants, h-2bm13 and h-2bm14. the ... | 1993 | 8452813 |
| immunology. tolerance by exhaustion. | | 1993 | 8469279 |
| virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector t cells. | viruses that are non- or poorly cytopathic have developed various strategies to avoid elimination by the immune system and to persist in the host. acute infection of adult mice with the noncytopathic lymphocytic choriomeningitis virus (lcmv) normally induces a protective cytotoxic t-cell response that also causes immunopathology. but some lcmv strains (such as docile (lcmv-d) or cl-13 armstrong (cl-13)) derived from virus carrier mice tend to persist after acute infection of adult mice without c ... | 1993 | 8469287 |
| regulation and function of host defences in the murine lymphocytic choriomeningitis virus infection. | | 1993 | 8472597 |
| a serologic survey for viruses and mycoplasma pulmonis among wild house mice (mus domesticus) in southeastern australia. | plasma samples from 267 wild house mice (mus domesticus) trapped at 14 sites in southeastern australia were screened for antibody to 14 viruses normally associated with laboratory-reared rodents and to mycoplasma pulmonis. serologic prevalence was high for murine cytomegalovirus (99%, n = 94), murine coronavirus (95%), and murine rotavirus (74%). samples from mice collected at all sites contained antibody to these viruses. the serologic prevalence was lower for mouse adenovirus, strain k87 (37%) ... | 1993 | 8487371 |
| induction of diabetes is influenced by the infectious virus and local expression of mhc class i and tumor necrosis factor-alpha. | to study self reactivity, a transgenic mouse model has been established in which the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) is expressed in the beta-islet cells of the pancreas (rat insulin promoter (rip)-gp). these mice (h-2b) do not spontaneously develop diabetes; however, infection with the lcmv strain we rapidly induces hyperglycemia. in this study, comparative analysis of h-2k rip-gp-transgenic animals demonstrated that the haplotype influences the incidence and kinetic ... | 1993 | 8496610 |
| alloreactive cytotoxic t cells can develop and function in mice lacking both cd4 and cd8. | using the technique of homologous recombination in embryonic stem cells, a mouse strain without functional cd4 and cd8 genes has been generated. surprisingly, these mice contain significant numbers of alpha beta t cells. although mice deficient for cd8 only do not show any cytotoxic response when their t cells are stimulated with either alloantigen or viral antigen, the cd4-8- mice do generate alloreactive cytotoxic t cells. these cytotoxic t cells bear the alpha beta t cell receptor and recogni ... | 1993 | 8500525 |
| elevated cerebrospinal fluid iga in humans and rats is not associated with secretory component. | immunoglobulin a (iga) is transported across mucosal tissue membranes covalently bound to secretory component (sc). to determine if this receptor-mediated process also occurs at central nervous system (cns) boundaries, cerebrospinal fluid (csf) and serum from patients with cns neuroinflammatory disease were analyzed for iga and sc. excess csf iga was detected in six of 24 patients, but no significant csf sc was detected. in a parallel study using a rat model with normal brain barriers, inactivat ... | 1993 | 8505403 |
| vaccination to prevent persistent viral infection. | persistent virus infections are increasingly being recognized as a significant cause of human morbidity and mortality. to establish persistence, a virus must establish infection and evade eradication by the host immune response, in particular by cytotoxic t lymphocytes (ctl). we have studied a virus that establishes persistence in part by suppressing the ctl response of the infected host. the virus persists in many cell types, including lymphocytes and macrophages. we show that prior immunizatio ... | 1993 | 8510226 |
| antiviral immune responses of mice lacking mhc class ii or its associated invariant chain. | induction of t-helper cells and t-b cell interaction have been considered to critically depend upon recognition of major histocompatibility complex (mhc) class ii molecules by the t cell receptor. mice lacking either mhc class ii molecules (class ii(0/0) mice) or its associated invariant chain (ii0/0 mice) provide new opportunities to test this premise. immune responses to some protein antigens have been studied in these mice; little is known about their ability to withstand viral infections. we ... | 1996 | 8548834 |
| the cd45rb-associated epitope defined by monoclonal antibody cz-1 is an activation and memory marker for mouse cd4 t cells. | monoclonal antibody cz-1 defines a novel sialic acid-dependent cd45rb-associated epitope. the cz-1 antigen is expressed on the subpopulation of cd4 t cells that proliferate in response to il-2. because il-2 responsiveness often denotes t cell activation, we examined the expression of the cz-1 antigen on cd4 t cells taken from mice at various times during an infection with lymphocytic choriomeningitis virus (lcmv). the blast-sized cd4 t cells at day 6 postinfection were cz-1+. further cell surfac ... | 1996 | 8548845 |