The Frequency of α4β7high Memory CD4+ T Cells Correlates With Susceptibility to Rectal Simian Immunodeficiency Virus Infection

Background: Integrin alpha(4)beta(7) (alpha(4)beta(7)) 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 alpha(4)beta(7) and during acute infection SIV preferentially infects alpha(4)beta(7) 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 alpha(4)beta(+)(7) 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 alpha(4)beta(7) (alpha(4)beta(high)(7) 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 alpha(4)beta(7) high memory CD4(+) T cells in blood and rectum before and after challenge. The frequency of alpha(4)beta(+)(7) myeloid DCs and alpha(4)beta(7) 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 alpha(4)beta(high)(7) CD4(+) T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.