Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection

One of the consequences of IIIV infection is damage to the CNS. To characte rize the virologic, immunologic, and functional factors involved in HIV-ind uced CNS disease, we analyzed the viral loads and T cell infiltrates in the brains of SIV-infected rhesus monkeys whose CNS function (sensory evoked p otential) was impaired. Following infection, CNS evoked potentials were abn ormal, indicating early CNS disease. Upon autopsy at I I wk post-SIV inocul ation, the brains of infected animals contained over 5-fold more CD8(+) T c ells than did uninfected controls. In both infected and uninfected groups, these CD8+ T cells presented distinct levels of activation markers (CD11a a nd CD95) at different sites: brain > CSF > spleen = blood > lymph nodes. Th e CD8+ cells obtained from the brains of infected monkeys expressed mRNA fo r cytolytic and proinflammatory molecules, such as granzymes A and B, perfo rin, and IFN-gamma. Therefore, the neurological dysfunctions correlated wit h increased numbers of CD8(+) T cells of an activated phenotype in the brai n, suggesting that virus-host interactions contributed to the related CNS f unctional defects.