Circulating integrin α4β7+ CD4 T cells are enriched for proliferative transcriptional programs in HIV infection

Abstract

HIV preferentially infects α4β7+ CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α4β7+ CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian–human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α4β7+ CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal α4β7+ CD4 T cells exhibited a core tissue-residency gene expression program. These features were conserved across primate species, indicating that the environment influences memory T-cell transcriptional networks. Our findings provide an important molecular foundation for understanding the role of α4β7 in HIV infection.