Article

Mucosal Immunology (2010) 3, 172–181; doi:10.1038/mi.2009.129; published online 2 December 2009

Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels

E J Ciccone1, S W Read2, P J Mannon3, M D Yao4, J N Hodge1, R Dewar5, C L Chairez1, M A Proschan6, J A Kovacs7 and I Sereti1

  1. 1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
  2. 2The Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
  3. 3Division of Gastroenterology and Hepatology, University of Alabama-Birmingham, Birmingham, Alabama, USA
  4. 4Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
  5. 5SAIC-Frederick Inc., Frederick, Maryland, USA
  6. 6The Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
  7. 7The Critical Care Medicine Department, NIH, Bethesda, Maryland, USA

Correspondence: I Sereti, (isereti@niaid.nih.gov)

Received 2 July 2009; Accepted 13 October 2009; Published online 2 December 2009.

Top

Abstract

The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samples were collected from viremic, untreated, HIV-infected participants, patients treated with prolonged ART (>5 years), and uninfected controls and analyzed by flow cytometry. In the gut, the proportion of cycling T cells decreased and the number of CD4+ T cells normalized in treated patients in parallel with β7 expression on CD4+ T cells in blood. Cycling of gut T cells in viremic patients was associated with increased plasma LPS levels, but not colonic HIV–RNA. These data suggest that gut T-cell activation and microbial translocation may be interconnected whereas prolonged ART may decrease activation and restore gut CD4+ T cells.