<i>CD101</i> genetic variants modify regulatory and conventional T cell phenotypes and functions.

Abstract

We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that <i>CD101</i> variants modify the prevalence of circulating inflammatory cell types and show that <i>CD101</i> variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of <i>CD101</i> variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with <i>CD101</i> variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with <i>CD101</i> variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.