TY - JOUR
T1 - 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
AU - Sachdeva, Naresh
AU - Weinstein, Jessica E.
AU - Ashman, Margarita
AU - Sachdeva, Meenakshi
AU - Brewer, Toye H.
AU - Gracia, Deborah
AU - Asthana, Deshratn
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/2/1
Y1 - 2010/2/1
N2 - 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-γ, a lower percentage of perforin and granzyme-B-producing CD8 T cells, and poor differentiation of effector memory CD8 TEM cells into CD8 TEMRA 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.
AB - 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-γ, a lower percentage of perforin and granzyme-B-producing CD8 T cells, and poor differentiation of effector memory CD8 TEM cells into CD8 TEMRA 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.
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U2 - 10.1089/vim.2009.0069
DO - 10.1089/vim.2009.0069
M3 - Article
C2 - 20121402
AN - SCOPUS:76449113777
VL - 23
SP - 49
EP - 61
JO - Viral Immunology
JF - Viral Immunology
SN - 0882-8245
IS - 1
ER -