Monitoring alpha4beta7 integrin expression on circulating CD4+ T cells as a surrogate marker for tracking intestinal CD4+ T-cell loss in SIV infection.
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 alpha4beta7 for attachment and signaling of CD4+ T cells, suggesting this molecule may have a central role in HIV pathogenesis. Here, we compared beta7(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 beta7(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 alpha4beta7 has a role in the selective depletion of intestinal CD4+ T cells, and indicate that monitoring beta7(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.
Wang
X
X
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA.
Xu
H
H
Gill
A F
AF
Pahar
B
B
Kempf
D
D
Rasmussen
T
T
Lackner
A A
AA
Veazey
R S
RS
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000276:immunology; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis* / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*
D015415:Biomarkers; D016023:Integrins; C071777:integrin alpha4beta7