The acute inflammatory process in murine lymphocytic choriomeningitis is dependent on Lyt-2+ immune T cells☆
Abstract
Virus-immune spleen cells induce fatal immunopathology following adoptive transfer into adult C57B1/6J mice that have been infected with lymphocytic choriomeningitis virus (LCMV) and immunosuppressed with cyclophosphamide. This is accompanied by the development of potent cytotoxic T-lymphocyte (CTL) activity of donor origin in the recipient spleen. Both the capacity to trigger the acute meningitis observed at 72 hr and to generate CTL effectors in lymphoid tissue are completely abrogated by the removal of Lyt-2+ cells from the donor population. However a lower level of inflammatory process in the central nervous system may emerge, in the absence of significant CTL function in recipient spleen, by 5 days after transfer of the Lyt-2-depleted cell population. Treatment of the transferred cells with antibody to the L3T4 marker does not reduce either the severity of inflammation or the level of CTL effector function in the recipient. Thus Lyt-2+ cells are required for the acute, fatal immunopathology characteristic of LCM, but it is not clear that in a more chronic situation, they are the sole effectors capable of triggering inflammatory process in this disease.
References (12)
- J.E. Allan et al.
Cell. Immunol
(1985) - P.C. Doherty et al.
J. Immunol
(1976) - S.L. Swain
Immunol. Rev
(1983) - J.E. Allan et al.
Scand. J. Immunol
(1985) - P.C. Doherty et al.
Scand. J. Immunol
(1983) - M. Sarmiento et al.
J. Immunol
(1980)
Cited by (34)
Lymphocytic Choriomeningitis Virus
2007, The Mouse in Biomedical ResearchLymphocytic choriomeningitis virus (LCMV) is an important virus of the laboratory mouse from a number of perspectives. Foremost is its well-documented zoonotic potential for humans. Mus musculus and its various aboriginal and commensal species or subspecies represent the natural reservoir hosts for LCMV, with an intimate host-virus relationship. This relationship may involve subclinical persistent infection that is associated with minimal or undetectable levels of circulating antibody; thus, detection of infection can be a challenge. LCMV infects a wide variety of tissues, and infection of mice can have protean effects upon normal physiology and immune response, with deleterious impact upon research. The polytropism of LCMV and its noncytolytic course of infection contribute to a well-deserved reputation as a cryptic contaminant of tumors and cell lines. This chapter emphasizes the biology of LCMV as a naturally occurring infection of laboratory mice and the practical consequences of infection. Experimental studies provide insight into understanding the biology of natural infection and are therefore reviewed.
Lymphocytic Choriomeningitis Virus
2006, The Mouse in Biomedical Research: History, Wild Mice, and Genetics: Volume 1-4, Second EditionLymphocytic choriomeningitis virus (LCMV) is an important virus of the laboratory mouse from a number of perspectives. Foremost is its well-documented zoonotic potential for humans. Mus musculus and its various aboriginal and commensal species or subspecies represent the natural reservoir hosts for LCMV, with an intimate host-virus relationship. This relationship may involve subclinical persistent infection that is associated with minimal or undetectable levels of circulating antibody; thus, detection of infection can be a challenge. LCMV infects a wide variety of tissues, and infection of mice can have protean effects upon normal physiology and immune response, with deleterious impact upon research. The polytropism of LCMV and its noncytolytic course of infection contribute to a well-deserved reputation as a cryptic contaminant of tumors and cell lines. This chapter emphasizes the biology of LCMV as a naturally occurring infection of laboratory mice and the practical consequences of infection. Experimental studies provide insight into understanding the biology of natural infection and are therefore reviewed.
DNA immunization and central nervous system viral infection
2001, Advances in Virus ResearchThis chapter discusses the virus infections of the central nervous system (CNS) and DNA vaccines. Mild central nervous system (CNS) symptoms, such as headache and drowsiness, can result from systemically elevated cytokine levels and therefore are common in many virus infections, even in the absence of the infection of the CNS. CNS infection is quite unusual and is initiated either as a result of the viremia or, more rarely, as a result of neural spread. The poliovirus infects the anterior horn motor neurons of the spinal cord, causing poliomyelitis, the disease for which the virus is named. DNA vaccination is a relatively new entrant in the vaccine sweepstakes, but is viewed with optimism, for a number of reasons. DNA vaccines encoding the nucleoprotein from lymphocytic choriomeningitis virus can confer protection against the normally lethal intracranial challenge. In rabies, in a mouse model, immunization with plasmids encoding the rabies glycoprotein conferred complete protection against subsequent viral challenge. Several virus-induced CNS diseases may be explained by their triggering of autoimmunity. Experimental autoimmune encephalomyelitis is a well-characterized CNS disease induced by the administration of certain CNS proteins.
Exacerbation of lymphocytic choriomeningitis in mice treated with the inducible nitric oxide synthase inhibitor aminoguanidine
1996, Journal of NeuroimmunologyTo elucidate the possible involvement of the inducible nitric oxide synthase (iNOS) and NO in the development of lymphocytic choriomeningitis (LCM), the consequences of inhibition of iNOS by the inhibitor aminoguanidine was examined in mice following intracerebral infection with LCM virus (LCMV). Aminoguanidine administration to mice infected with LCMV completely blocked increased plasma nitrate/nitrite levels and led to increased proinflammatory cytokine gene expression at early stages of lesion development in the brain, enhanced clinical severity and decreased survival time. The levels of LCMV recovered from the brain of aminoguanidine treated mice did not differ from those in infected control mice. These findings argue against either an anti-viral or pathogenic role of NO in LCM but rather suggest a possible protective action of this mediator.
Altered kinetics of CD4<sup>+</sup> T cell proliferation and interferon-γ production in the absence of CD8<sup>+</sup> T lymphocytes in virus-infected β2-microglobulin-deficient mice
1996, Cellular ImmunologyCD8+T cells are the major mediators of cytotoxic T cell activity controlling viral infections in normal mice. CD8+T cells have also been implicated in regulating the activity of other immune cells. We have examined the possible regulatory role of CD8+T cells on CD4+T cells by comparing immune responses in mice expressing normal CD8+T cell responses and in CD8+T cell-deficient β2-microglobulin “knockout” mice. In normal mice, infection with lymphocytic choriomeningitis virus (LCMV) results in a biphasic T cell immune response. First, CD8+T cells proliferate and produce interferon-γ (IFN-γ), and then 2 to 4 days later CD4+T cells proliferate and produce IFN-γ. CD8+T cell activity is not detected during LCMV infection in β2-microglobulin-deficient mice. However, in β2-microglobulin-deficient mice the CD4+T cell expansion is exaggerated and occurs 2 days earlier than observed in normal mice. Furthermore, the CD4+T cells have substantial cytotoxic activity, which is not observed in the CD4+T cell population in normal mice. However, CD4+T cell IFN-γ production in β2-microglobulin-deficient mice lags behind the proliferative response, resulting in a relative delay in overall T cell IFN-γ production compared to normal mice. Taken together, these data suggest that CD8+T cell activation peaks at an earlier time point than CD4+T cell activation during the primary immune response to LCMV and that CD8+T cells may inhibit CD4+T cell proliferation and the development of CD4+T cell cytotoxic activity.
Teratogenic effects of neonatal arenavirus infection on the developing rat cerebellum are abrogated by passive immunotherapy
1993, VirologyThe 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 and internal granular layers of LCMV-infected cerebella were noticeably thinner than those in the controls and the individual folia were smaller. Neurons remained infected for up to 40 days as determined by immunohistochemistry. However, in rats treated with rat monoclonal anti-LCMV antibodies the staining was limited to the cells of ependyma and choroid plexus and was not detectable by 15 days postinfection. Macroscopically the infection resulted in pronounced hypoplasia, with the cerebella of 21-day-old LCMV-infected rats weighing 52 ± 10 mg compared with 159 ± 30 mg for control rats. Antibody-treated rats exhibited normal cerebellar size and development. Neutralizing antibodies specific for the viral GP-1 glycoprotein were protective but nucleoprotein-specific antibodies were not. Furthermore, suckling rat pups born of and nursed by LCMV-immune mothers were spared from cerebellar disease following neonatal infection. These results suggest that passive immunotherapy of neonates can provide effective protection against teratogenic effects of neonatal viral infection on the developing CNS.
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Supported in part by Grant AI19455 from the US National Institutes of Health.