Background: Integrin α4β7 (α4β7) 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 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 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 (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, whereas 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.
*Center for Biomedical Research, Population Council, New York, NY;
†Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
‡AIDS and Cancer Virus Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD;
§Tulane National Primate Research Center, Tulane University Sciences Center, Covington, LA; and
‖Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY.
Correspondence to: Elena Martinelli, PhD, MPH, Center for Biomedical Research, Population Council, 1188 York Avenue, New York, NY 10065 (e-mail firstname.lastname@example.org).
Supported by NIH Grant R37 AI040877-15.
The authors have no conflicts of interest to disclose.
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Received March 19, 2013
Accepted June 06, 2013