title: Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults.
abstract: Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.
authors: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, United States of America; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Steven A
authors: SA
authors: Yukl
authors: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, United States of America; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Amandeep K
authors: AK
authors: Shergill
authors: Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Valerie
authors: V
authors: Girling
authors: School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
authors: Qingsheng
authors: Q
authors: Li
authors: Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Maudi
authors: M
authors: Killian
authors: Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Lorrie
authors: L
authors: Epling
authors: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, United States of America; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Peilin
authors: P
authors: Li
authors: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, United States of America; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Philipp
authors: P
authors: Kaiser
authors: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Ashley
authors: A
authors: Haase
authors: Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Diane V
authors: DV
authors: Havlir
authors: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, United States of America; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Kenneth
authors: K
authors: McQuaid
authors: Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Elizabeth
authors: E
authors: Sinclair
authors: Department of Medicine, San Francisco VA Medical Center, San Francisco, California, United States of America; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California, United States of America.
authors: Joseph K
authors: JK
authors: Wong
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D041981:Gastrointestinal Tract / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers