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Session 97 Poster Session Neuropathogenesis Session Time: 4:30-6:30 pm Room 4E-F

733-W. Changes in Cell Adhesion Molecule and Chemokine Receptor Expression on HIV-Specific CTL Migrating to Cerebrospinal Fluid R. W. Price*1, C. A. Cox2, D. T. Wilkens2, J. Neuenburg2, A. Nilsson1, D. F. Nixon2, and B. L. Shacklett2 1San Francisco Gen. Hosp. and 2Gladstone Inst. of Virology and Immunology, Univ. of California, San Francisco, CA Background: HIV-specific cytotoxic T cells (CTL) localized to the central nervous system (CNS) may play an important role in immune surveillance, but might also contribute to neuropathogenesis via cytotoxicity and/or cytokine release. The mechanisms responsible for T-cell trafficking to the CNS are largely unknown. Methods: To better understand the mechanisms driving recruitment of HIV-specific CTL to the CNS, we used multiparameter flow cytometry to study expression of lymphocyte adhesion molecules VLA-4, LFA-1, and chemokine receptors CXCR3, CXCR4, and CCR5 on HIV-specific CD8+ T cells in peripheral blood and cerebrospinal fluid of 3 HIV-infected individuals. Results: While both CD4+ and CD8+ T-cells in peripheral blood exhibited a bimodal expression pattern of LFA-1, T-cells trafficking to CSF were predominantly VLA-4high, LFA-1high. CD8+ T cells in CSF also expressed increased levels of CXCR3 and CCR5 relative to those in peripheral blood, suggesting a role for these receptors and their ligands in T-cell recruitment to the CNS. In 2 HIV-positive individuals, CD8+ Tcells specific for the HIV Gag (p17, 77-85) epitope SLYNTVATL were present at similar frequencies in peripheral blood and CSF. In CSF, these CTL expressed predominantly CD45RO and were CCR5high. Conclusions:These results suggest that CTL trafficking to the CNS are highly activated, express high levels of adhesion molecules VLA-4 and LFA-1 and chemokine receptors CXCR3 and CCR5, and that recruitment pathways for HIV-specific T cells may be similar to those observed in other inflammatory diseases of the central nervous system, including multiple sclerosis.

©2002 9th Conference on Retroviruses and Opportunistic Infections