HIV-specific IL-10-positive CD8+ T cells are increased in advanced disease and are associated with decreased HIV-specific cytolysis.
IL-10-producing T cells have been shown to inhibit Ag-specific CD8+ T cell responses, and may play a role in the immune dysregulation observed in HIV-1 infection. We characterized the Gag-specific IL-10 responses by CD8+ T cells in HIV-1-positive volunteers from Uganda. HIV-specific IL-10 responses were detected in 32 of 61 (52.4%) antiretroviral naive and 2 of 15 (13.3%) volunteers with a complete virologic response on antiretroviral therapy (< 400 copies/ml). The frequency of HIV-specific IL-10-positive cells was significantly higher in volunteers with advanced disease (CD4+ T cell count <200 cells/mm3; p = 0.0004), and correlated positively with plasma HIV RNA (r = 0.43, p = 0.0004). Interestingly, the frequency of Gag-specific CD107a/b-, but not IFN-gamma-, positive cells was significantly lower in individuals with detectable IL-10-positive CD8+ T cells (p = 0.004). Gag-specific IL-10-positive CD8+ T cells demonstrated a pattern of surface memory marker expression that is distinct compared with CD107a/b- and IFN-gamma-positive CD8+ T cell populations (p < 0.0001). Our study describes a distinct population of IL-10-positive CD8+ T cells that may play a role in HIV-associated immune dysfunction.
Elrefaei
Mohamed
M
California Department of Health Services, Richmond, CA 94804, USA. melrefae@dhs.ca.gov
Barugahare
Banson
B
Ssali
Francis
F
Mugyenyi
Peter
P
Cao
Huyen
H
D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D014454:Uganda
D015683:Gene Products, gag; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D012367:RNA, Viral; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma