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/mm(3); 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.