The frequency of α₄β₇(high) memory CD4⁺ T cells correlates with susceptibility to rectal simian immunodeficiency virus infection.

Abstract

BACKGROUND: Integrin α₄β₇(high) (α₄β₇(high)) mediates the homing of CD4⁺ T cells to gut-associated lymphoid tissues, which constitute a highly favorable environment for HIV expansion and dissemination. HIV and simian immunodeficiency virus (SIV) envelope proteins bind to and signal through α₄β₇(high) and during acute infection SIV preferentially infects α₄β₇(high) CD4⁺ T cells. We postulated that the availability of these cells at the time of challenge could influence mucosal SIV transmission and acute viral load (VL). METHODS: We challenged 17 rhesus macaques with 3000 TCID50 of SIVmac239 rectally and followed the subsets of α₄β₇(high) T cells and dendritic cells (DCs) by flow cytometry in blood and tissues, before and after challenge. RESULTS: We found that the frequency of memory CD4⁺ T cells that expressed high levels of α₄β₇(high) (α₄β₇(high) memory CD4⁺ T cells) in blood before challenge correlated strongly with susceptibility to infection and acute VL. Notably, not only at the time of challenge but also their frequency 3 weeks before challenge correlated with infection. This association extended to the rectal tissue as we observed a strong direct correlation between the frequency of α₄β₇(high) memory CD4⁺ T cells in blood and rectum before and after challenge. The frequency of α4β7 myeloid DCs and α₄β₇(high) CD80⁺ DCs also correlated with infection and acute VL, whereas blood CCR5⁺ and CD69⁺ CD4⁺ T cells could not be associated with infection. CONCLUSIONS: Our results suggest that animals with higher frequency of α₄β₇(high) CD4⁺ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.