Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection. |
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Authors: | M C Marcondes E M Burudi S Huitron-Resendiz M Sanchez-Alavez D Watry M Zandonatti S J Henriksen H S Fox |
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Affiliation: | Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. |
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Abstract: | One of the consequences of HIV infection is damage to the CNS. To characterize the virologic, immunologic, and functional factors involved in HIV-induced CNS disease, we analyzed the viral loads and T cell infiltrates in the brains of SIV-infected rhesus monkeys whose CNS function (sensory evoked potential) was impaired. Following infection, CNS evoked potentials were abnormal, indicating early CNS disease. Upon autopsy at 11 wk post-SIV inoculation, the brains of infected animals contained over 5-fold more CD8(+) T cells than did uninfected controls. In both infected and uninfected groups, these CD8(+) T cells presented distinct levels of activation markers (CD11a and CD95) at different sites: brain > CSF > spleen = blood > lymph nodes. The CD8(+) cells obtained from the brains of infected monkeys expressed mRNA for cytolytic and proinflammatory molecules, such as granzymes A and B, perforin, and IFN-gamma. Therefore, the neurological dysfunctions correlated with increased numbers of CD8(+) T cells of an activated phenotype in the brain, suggesting that virus-host interactions contributed to the related CNS functional defects. |
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