Association of IL-10-promoter genetic variants with the rate of CD4 T-cell loss, IL-10 plasma levels, and breadth of cytotoxic t-cell lymphocyte response during chronic HIV-1 infection

摘要

Background. Interleukin-10 (IL-10) is a potent immunoregulatory cytokine. IL-10-promoter polymorphisms have been shown to affect human immunodeficiency virus type 1 (HIV-1) clinical outcomes but the underlying mechanisms are poorly understood.Methods.We investigated the relationship between IL-10-promoter variants, plasma cytokine levels, immune responses and markers of disease outcome in antiretroviral-na?ve HIV-1 chronically infected individuals from South Africa. Two IL-10-promoter single nucleotide polymorphisms (SNPs) were genotyped in 451 participants. Baseline plasma levels of select cytokines were measured for 112 individuals. Viral load, CD4 + T-cell counts and HIV-1-specific interferon-gamma CD8 + T-cell immune responses were measured at baseline. CD4 + T-cell counts were measured longitudinally and rates of CD4 + T-cell decline computed for 300 study subjects. Results. The minor IL-10-1082G and-592A variants occurred at frequencies of 0.31 and 0.34, respectively. The-592AA genotype associated significantly with attenuated loss of CD4 + T cells (P=.0496). Individuals possessing-1082GG had significantly higher IL-10 levels compared to-1082AA/AG (P =. 0006). The-592AA genotype was associated with greater breadth of virus-specific CD8 + T-cell responses compared to CC and CA (P =. 002 and. 004 respectively).Conclusions.IL-10-promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels and the breadth of CD8 + T-cell immune responses.