The role of CD8(+) T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent Sindbis virus.
Little is known about the role of CD8(+) T cells infiltrating the neural parenchyma during encephalitis induced by neurovirulent Sindbis virus (NSV). NSV preferentially infects neurons in the mouse brain and spinal cord; however, it is generally accepted that neurons can express few if any major histocompatibility complex (MHC) class I molecules. We evaluated the possible roles and interactions of CD8(+) T cells during NSV encephalitis and demonstrated that MHC class I antigen (H2K/D) was expressed on endothelial cells, inflammatory cells, and ependymal cells after intracerebral inoculation of NSV. No immunoreactivity was observed in neurons. On the other hand, in situ hybridization with probes for MHC class I heavy chain, beta2 microglobulin, and TAP1 and TAP2 mRNAs revealed increased expression in a majority of neurons, as well as in inflammatory cells, endothelial cells, and ependymal cells in the central nervous system of infected mice. NSV-infected neurons may fail to express MHC class I molecules due to a posttranscriptional block or may express only nonclassical MHC class I genes. To better understand the role CD8(+) T cells play during fatal encephalitis induced by NSV, mice lacking functional CD8(+) T cells were studied. The presence or absence of CD8 did not alter outcome, but absence of beta2 microglobulin improved survival. Interestingly, the intracellular levels of viral RNA decreased more rapidly in immunocompetent mice than in mice without functional CD8(+) T cells. These observations suggest that CD8(+) T cells may act indirectly, possibly via cytokines, to contribute to the clearance of viral RNA in neurons.
Kimura
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W. Harry Feinstone Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Griffin
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D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000821:virology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000821:virology; D006224:Cricetinae; D005260:Female; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D017403:In Situ Hybridization / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D012845:Sindbis Virus; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology* / Q000821:virology; D014774:Virulence; D014779:Virus Replication; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D001613:beta 2-Microglobulin