Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults

Steven A. Yukl, Amandeep K. Shergill, Valerie Girling, Qingsheng Li, Maudi Killian, Lorrie Epling, Peilin Li, Philipp Kaiser, Ashley Haase, Diane V. Havlir, Kenneth McQuaid, Elizabeth Sinclair, Joseph K. Wong

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Article numbere0121290
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 26 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yukl, S. A., Shergill, A. K., Girling, V., Li, Q., Killian, M., Epling, L., Li, P., Kaiser, P., Haase, A., Havlir, D. V., McQuaid, K., Sinclair, E., & Wong, J. K. (2015). Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults. PloS one, 10(3), [e0121290]. https://doi.org/10.1371/journal.pone.0121290