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

HIV preferentially infects alpha(4)beta(+)(7) CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of alpha(4)beta(+)(7) 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 alpha(4)beta(+)(7) CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism. Unlike their circulating counterparts, rectal alpha(4)beta(+)(7) 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 alpha(4)beta(7) in HIV infection.

Automated summary

The study found that HIV preferentially infects alpha(4)beta(+)(7) CD4 T cells and enriches genes regulating cell cycle progression and cellular metabolism in the blood. Unlike their blood counterparts, rectal alpha(4)beta(+)(7) CD4 T cells exhibit a core tissue-residency gene expression program.