+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Critical Role of MHC Class I-Restricted Cytotoxicity in Viral Clearance and Immune-Mediated Neuropathology after Lymphocytic Choriomeningitis Virus Infection in Mice



Critical Role of MHC Class I-Restricted Cytotoxicity in Viral Clearance and Immune-Mediated Neuropathology after Lymphocytic Choriomeningitis Virus Infection in Mice



Blood 100(11): Abstract No. 449



In order to study T-cell lineage commitment, we have generated a mouse strain in which T cells cannot "switch off" CD4. This was achieved by deleting the silencer element in the first intron of the CD4 gene by a combination of homologous recombination and Cre-lox-mediated recombination in embryonic stem cells. The resultant mouse strain developed double positive mature T cells in the periphery. Functional assays revealed that some of these double positive cells were MHC class I-restricted while others were MHC class II-restricted and exhibited cytotoxic T cell (CTL) activity. In order to investigate the relative roles of MHC class I and class II cytotoxicity in anti-viral responses, we have bred these mice to mice deficient in MHC class I expression (beta-2 microglobulin deficient). These mice therefore had CTLs that were exclusively MHC class II-restricted. We infected wild-type mice (bearing class I-restricted CTLs), CD4-silencer-deficient mice (bearing class I- and II-restricted CTLs), CD4-silencer-deficient x beta-2 microglobulin-deficient mice (bearing class II-restricted CTLs) and beta-2 microglobulin-deficient mice (bearing no CTLs) with the non-cytopathic, lymphocytic choriomeningitis virus (LCMV) intravenously. beta-2 microglobulin-deficient mice and CD4-silencer-deficient x beta-2 microglobulin deficient were unable to clear the virus. Intracranial injection of LCMV caused immune-mediated neuropathology in wild-type mice and CD4-silencer-deficient mice but not in the double (CD4-silencer x beta-2 microglobulin) deficient or beta-2 microglobulin-deficient mice. This result shows that class I restricted CTLs are necessary for clearance of LCMV after intravenous injection of LCMV, and immune-mediated neuro-pathology after intracranial injection of LCMV. Therefore, for this non-cytopathic virus, viral epitopes are presented to CTLs only in the context of MHC class I.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 034661764

Download citation: RISBibTeXText


Related references

Cytolytically active memory CTL present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection. Journal of Immunology 158(11): 5366-5373, 1997

Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice. Journal of Virology 86(16): 8713-8719, 2012

Mechanism of recovery from acute virus infection 1. role of t lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice. Journal of Immunology 134(1): 608-615, 1985

Mechanism of recovery from acute virus infection. IV. Questionable role of mononuclear phagocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice. Journal of Immunology 138(7): 2282-2289, 1987

Infection of new born mice with lymphocytic choriomeningitis virus role of viral strain origin and congenital infection. Annales de Virologie (Paris) 132(3): 313-322, 1981

Stimulation of cell mediated immune response to infection with lymphocytic choriomeningitis virus in suckling mice. Acta Microbiologica Academiae Scientiarum Hungaricae 25(2): 153, 1978

T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay?. Journal of Experimental Medicine 164(4): 1075-1092, 1986

The association of HLA-DR13 with viral clearance in hepatitis B virus infection may be mediated by a more vigorous virus-specific HLA class II restricted T cell response. Hepatology 26(4 Part 2): 223A, 1997

Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. II. Relationship of the anti-lymphocytic choriomeningitis immune response to tissue injury in chronic lymphocytic choriomeningitis disease. Journal of Experimental Medicine 131(1): 1-19, 1970

Quantification of epitope-specific MHC class-II-restricted T cells following lymphocytic choriomeningitis virus infection. Cellular Immunology 193(2): 134-146, 1999

Perforin and Fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection. Journal of Virology 78(22): 12395-12405, 2004

Fatal central nervous system disease in lymphocytic choriomeningitis virus carrier mice given lymphocytic choriomeningitis virus immune donor spleen cells. Federation Proceedings 30(2): 353, 1971

Virus-specific, CD8+ major histocompatibility complex class I-restricted cytotoxic T lymphocytes in lymphocytic choriomeningitis virus-infected b2-microglobulin-deficient mice. Journal of Virology 71: 92-6, 1997

Virus-specific, CD8+ major histocompatibility complex class I-restricted cytotoxic T lymphocytes in lymphocytic choriomeningitis virus-infected beta2-microglobulin-deficient mice. Journal of Virology 71(11): 8392-8396, 1997

Virus specificity of cytotoxic T lymphocytes generated during acute lymphocytic choriomeningitis virus infection: role of the H-2 region in determining cross-reactivity for different lymphocytic choriomeningitis virus strains. Journal of Virology 51(1): 34-41, 1984