Journal
MUCOSAL IMMUNOLOGY
Volume 2, Issue 6, Pages 518-526Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2009.104
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Funding
- NIH [RR00164, AI049080, AA013563, AI062410]
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Intestinal CD4+ T cells are rapidly and profoundly depleted in human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV)-infected macaques. However, monitoring intestinal cells in humans is difficult, and identifying surrogate markers in the blood, which correlate with loss or restoration of intestinal CD4+ T cells could be helpful in monitoring the success of therapeutic strategies and vaccine candidates. Recent studies indicate HIV utilizes the intestinal homing molecule alpha 4 beta 7 for attachment and signaling of CD4+ T cells, suggesting this molecule may have a central role in HIV pathogenesis. Here, we compared beta 7(HIGH) integrin expression on CD4+ T cells in blood with loss of CD4+ T cells in the intestine of macaques throughout SIV infection. The loss of beta 7(HIGH) CD4+ T cells in blood closely paralleled the loss of intestinal CD4+ T cells, and proved to be a more reliable marker of intestinal CD4+ T-cell loss than monitoring CCR5+ memory CD4+ T cells. These data are consistent with a recent hypothesis that alpha 4 beta 7 has a role in the selective depletion of intestinal CD4+ T cells, and indicate that monitoring beta 7(HIGH) expression on CD4+ T cells in the blood may be a useful surrogate for estimating intestinal CD4+ T cell loss and restoration in HIV-infected patients.
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