Quantitative and Qualitative Assessment of Human Immunodeficiency Virus Type 1 (HIV-1)–Specific CD4+ T Cell Immunity to gag in HIV-1–Infected Individuals with Differential Disease Progression: Reciprocal Interferon-γ and Interleukin-10 Responses

The human immunodeficiency virus type 1 (HIV-1)–specific CD4+ T cell response was investigated in 33 untreated HIV-1–infected individuals, using highly sensitive ELISPOT assays and intracellular flow cytometry. The median frequencies of interferon (IFN)–γ–producing HIV-1 gag–specific CD4+ T cells did not correlate significantly with control of viral replication or progression. HIV-1 gag–specific interleukin (IL)–4–producing cells were rarely detected. Circulating frequencies of CD4+ T cells constitutively producing IL-10, however, were significantly higher in individuals with progression or active replication. In 17 of 30 HIV-1–infected individuals, gag antigen was observed to induce IL-10 production from CD4+ T cells. In 2 individuals, early treatment of acute HIV-1 infection “rescued” low to undetectable gag-specific IFN-γ–producing CD4+ T cell responses and dramatically down-regulated constitutive IL-10 production from circulating CD4+ T cells. The detection of HIV-1–specific IL-10–inducing CD4+ T cells in HIV-1–infected individuals suggests that HIV-1 may directly subvert specific immune responses by IL-10 induction