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

Integrin α&sub4;β₇(high) (α&sub4;β₇(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 α&sub4;β₇(high) and during acute infection SIV preferentially infects α&sub4;β₇(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).

Our results suggest that animals with higher frequency of α&sub4;β₇(high) CD4⁺ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.

We challenged 17 rhesus macaques with 3000 TCID50 of SIVmac239 rectally and followed the subsets of α&sub4;β₇(high) T cells and dendritic cells (DCs) by flow cytometry in blood and tissues, before and after challenge.

We found that the frequency of memory CD4⁺ T cells that expressed high levels of α&sub4;β₇(high) (α&sub4;β₇(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 α&sub4;β₇(high) memory CD4⁺ T cells in blood and rectum before and after challenge. The frequency of α4β7 myeloid DCs and α&sub4;β₇(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 α&sub4;β₇(high) CD4⁺ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.