The Frequency of 47high Memory CD4+ T Cells Correlates With Susceptibility to Rectal Simian Immunodeficiency Virus Infection

Martinelli, Elena PhD, MPH*; Veglia, Filippo PhD*; Goode, Diana PhD*; Guerra-Perez, Natalia PhD*; Aravantinou, Meropi MS*; Arthos, James PhD; Piatak, Michael Jr DMV, PhD; Lifson, Jeffrey D. MD; Blanchard, James PhD§; Gettie, Agegnehu BS; Robbiani, Melissa PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 December 2013 - Volume 64 - Issue 4 - p 325–331
doi: 10.1097/QAI.0b013e31829f6e1a
Basic and Translational Science

Background: Integrin α4β74β7) 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 α4β74β7high 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 emartinelli@popcouncil.org).

Supported by NIH Grant R37 AI040877-15.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jaids.com).

Received March 19, 2013

Accepted June 06, 2013

© 2013 by Lippincott Williams & Wilkins