title: Poor lymphoproliferative responses with low proportion of Gag-specific CD8 TEMRA cells in HIV-1-infected patients showing immunological and virological discordance despite prolonged suppression of plasma viremia.
abstract: We investigated in-vitro lymphoproliferative responses and T-cell subsets in 38 HIV-1-infected patients showing impaired restoration of CD4 T cells despite prolonged viral suppression (discordant), and in 42 HIV-1-infected patients showing positive immunological and virological responses to highly active antiretroviral therapy (HAART) (concordant). In comparison to concordant patients, discordant patients showed poor lymphocyte proliferation, lower secretion of IL-2 and IFN-gamma, a lower percentage of perforin and granzyme-B-producing CD8 T cells, and poor differentiation of effector memory CD8 T(EM) cells into CD8 T(EMRA) cells in in-vitro stimulation assays, especially against HIV-1 Gag p24 and one of its peptide pools. Functional CD8 T-cell responses of discordant patients after stimulation with recall antigens, Candida albicans, and tetanus toxoid, were also inferior to concordant patients, but comparable to normal healthy controls. Examination of the multifunctional roles of T cells is imperative in describing the overall magnitude of immune responses to HIV-1. Our results suggest that prolonged suppression of plasma viremia alone does not warrant good qualitative and quantitative CD8 T-cell responses to HIV-1, implying that CD4 T cells are required for maintenance of protective CD8 T-cell responses.
authors.affiliation: Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, Florida 33136, USA.
authors.forename: Naresh
authors.initials: N
authors.lastname: Sachdeva
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Weinstein
authors.forename: Margarita
authors.initials: M
authors.lastname: Ashman
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Sachdeva
authors.forename: Toye H
authors.initials: TH
authors.lastname: Brewer
authors.forename: Deborah
authors.initials: D
authors.lastname: Gracia
authors.forename: Deshratn
authors.initials: D
authors.lastname: Asthana
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D019562:Viral Load; D014766:Viremia; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D013745:Tetanus Toxoid; D054301:gag Gene Products, Human Immunodeficiency Virus