Article
Mucosal Immunology (2008) 1, 49–58. doi:10.1038/mi.2007.5
High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage
J M Brenchley1,7, K S Knox2,3,7, A I Asher1, D A Price1,4, L M Kohli2, E Gostick4, B J Hill1, C A Hage2,3, Z Brahmi5, A Khoruts6, H L Twigg III2, T W Schacker6 and D C Douek1
- 1Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
- 2Division of Pulmonary and Critical Care Medicine, Indiana University, Indianapolis, Indiana, USA
- 3Richard L Roudebush VA Medical Center, Indianapolis, Indiana, USA
- 4Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
- 5Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana, USA
- 6Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
Correspondence: DC Douek or JM Brenchley, (ddouek@mail.nih.gov)
7These authors contributed equally to this work.
Received 27 February 2007; Accepted 31 July 2007.
Abstract
The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to illuminate the pathogenesis of HIV-associated disease. Here, we studied depletion and HIV infection frequencies of CD4 T cells from the gastrointestinal tract, bronchoalveolar lavage (BAL), and blood with the frequencies and functional profiles of HIV-specific T cells in these anatomically distinct sites in HIV-infected individuals. The major findings to emerge were as follows: (i) depletion of gastrointestinal CD4 T cells is associated with high frequencies of infected CD4 T cells; (ii) HIV-specific T cells are present at low frequencies in the gastrointestinal tract compared to blood; (iii) BAL CD4 T cells are not massively depleted during the chronic phase; (iv) infection frequencies of BAL CD4 T cells are similar to those in blood; (v) significantly higher frequencies and increased functionality of HIV-specific T cells were observed in BAL compared to blood. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells.
