Monitoring α4β7 integrin expression on circulating CD4+ T cells as a surrogate marker for tracking intestinal CD4+ T-cell loss in SIV infection

Abstract

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 α4β7 for attachment and signaling of CD4+ T cells, suggesting this molecule may have a central role in HIV pathogenesis. Here, we compared β7HIGH 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 β7HIGH 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 α4β7 has a role in the selective depletion of intestinal CD4+ T cells, and indicate that monitoring β7HIGH 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.