title: Monitoring alpha4beta7 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 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.
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: A F
authors.initials: AF
authors.lastname: Gill
authors.forename: B
authors.initials: B
authors.lastname: Pahar
authors.forename: D
authors.initials: D
authors.lastname: Kempf
authors.forename: T
authors.initials: T
authors.lastname: Rasmussen
authors.forename: A A
authors.initials: AA
authors.lastname: Lackner
authors.forename: R S
authors.initials: RS
authors.lastname: Veazey
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D016023:Integrins; C071777:integrin alpha4beta7