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 pa renchyma during encephalitis induced by neurovirulent Sindbis virus (NSV), NSV preferentially infects neurons in the mouse brain and spinal cord; howe ver, it is generally accepted that neurons can express few if any major his tocompatibility complex (MHC) class I molecules. We evaluated the possible roles and interactions of CD8(+) T cells during NSV encephalitis and demons trated 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 si tu hybridization with probes for MHC class I heavy chain, beta 2 microglobu lin, and TAP1 and TAP2 mRNAs revealed increased expression in a majority of neurons, as well as in inflammatory cells, endothelial cells, and ependyma l cells in the central nervous system of infected mice. NSV-infected neuron s may fail to express MHC class I molecules due to a posttranscriptional bl ock or may express only nonclassical MHC class I genes. To better understan d the role CD8(+) T cells play during fatal encephalitis induced by NSV, mi ce lacking functional CD8(+) T cells were studied. The presence or absence of CD8 did not alter outcome, but absence of beta 2 microglobulin improved survival, Interestingly, the intracellular levels of viral RNA decreased mo re 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 neur ons.