CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions

Cell Rep Med. 2021 Jun 15;2(6):100322. doi: 10.1016/j.xcrm.2021.100322.


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 CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 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 CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

Keywords: CD101; HIV acquisition; T cell; host genetic variation; immune quiescence; inflammation; inflammatory homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • Cell Lineage / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / virology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunity, Innate
  • Immunophenotyping
  • Male
  • Monocytes / immunology
  • Monocytes / virology
  • Mutation*
  • Phenotype
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / immunology
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / virology


  • Antigens, CD
  • CCR5 protein, human
  • CXCR4 protein, human
  • Cd101 protein, mouse
  • Receptors, CCR5
  • Receptors, CXCR4