title: Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection.
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.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Marcondes
authors.forename: E M
authors.initials: EM
authors.lastname: Burudi
authors.forename: S
authors.initials: S
authors.lastname: Huitron-Resendiz
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: D
authors.initials: D
authors.lastname: Watry
authors.forename: M
authors.initials: M
authors.lastname: Zandonatti
authors.forename: S J
authors.initials: SJ
authors.lastname: Henriksen
authors.forename: H S
authors.initials: HS
authors.lastname: Fox
mesh_terms: D015526:AIDS Dementia Complex / Q000209:etiology*; D000818:Animals; D001921:Brain / Q000276:immunology*; D001927:Brain Diseases / Q000209:etiology*; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology*; D019014:fas Receptor / Q000032:analysis
chemical_list: D018106:CD28 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D019014:fas Receptor