The frequency of α4β7high memory CD4+ T cells correlates with susceptibility to rectal simian immunodeficiency virus infection
Background: Integrin α4β7 (α4β7) mediates the homing of CD4+ T cells to gut-associated lymphoid tissues (GALT), which constitute a highly favorable environment for HIV expansion and dissemination. HIV and SIV envelope proteins bind to and signal through α4β7 and during acute infection SIV preferentially infects α4β7high 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+ T 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 (α4β7high 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 α4β7high memory CD4+ T cells in blood and rectum before and after challenge. The frequency of α4β7+ myeloid DCs and α4β7high CD80+ DCs also correlated with infection and acute VL, while blood CCR5+ and CD69+ CD4+ T cells could not be associated with infection. Conclusions: Our results suggest that animals with higher frequency of α4β7high CD4+ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.
Martinelli, Elena, Filippo Veglia, Diana J. Goode, Natalia Guerra-Perez, Meropi Aravantinou, James Arthos, Michael Piatak Jr., Jeffrey D. Lifson, James Blanchard, Agegnehu Gettie, and Melissa Robbiani. 2013. "The frequency of α4β7high memory CD4+ T cells correlates with susceptibility to rectal simian immunodeficiency virus infection," Journal of Acquired Immune Deficiency Syndromes 64(4): 325–331.