title: Presence of distinct subsets of cytolytic CD8+ T cells in chronic HIV infection.
abstract: Cytolytic T lymphocytes (CTL) play an important role in the control of HIV infection. The eventual failure to contain HIV-1 infection may arise because of a functional impairment of HIV-specific CTL. We evaluated Gag-specific cytotoxicity in HIV-1-positive Ugandans. Expression of CD107, a marker for cytolytic activity, was present in CD45RA(bright) and CD45RA(dim) CD8(+) T cell populations in HIV-infected individuals. The frequency of Gag-specific CD107(+)CD45RA(bright)CD28(-)CCR7(-) CD8(+) T cells decreased with CD4 cell depletion and correlated with the presence of Gag-specific T helper response. In contrast, the frequency of Gag-specific CD107(+)CD45RA(dim)CD28(-)CCR7(-) CD8(+) T cells within the same individuals has no significant association with viral load or CD4 cell count. The ratio of CD45RA(bright) to CD45RA(dim) CTL correlates significantly with CD4 cell count. This positive association decreases with antiretroviral treatment (ARV), indicating that suppression of viral replication alters the balance of circulating Gag-specific CD8(+) effector T cells. Subsets of cytolytic T cells may have distinct antiviral functions and further characterization of these effector CD8(+) T cells may yield important information on T cell regulation and dysfunction in HIV infection.
authors.affiliation: California Department of Health Services, Richmond, California 94804, USA. njones@dhs.ca.gov
authors.forename: Norman
authors.initials: N
authors.lastname: Jones
authors.forename: Mark
authors.initials: M
authors.lastname: Eggena
authors.forename: Chris
authors.initials: C
authors.lastname: Baker
authors.forename: Frehd
authors.initials: F
authors.lastname: Nghania
authors.forename: David
authors.initials: D
authors.lastname: Baliruno
authors.forename: Peter
authors.initials: P
authors.lastname: Mugyenyi
authors.forename: Francis
authors.initials: F
authors.lastname: Ssali
authors.forename: Banson
authors.initials: B
authors.lastname: Barugahare
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000145:classification* / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification*; D014454:Uganda
chemical_list: D044966:Anti-Retroviral Agents; D052118:Lysosomal-Associated Membrane Protein 1; D017493:Leukocyte Common Antigens