High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage

J. M. Brenchley, Kenneth S Knox, A. I. Asher, D. A. Price, L. M. Kohli, E. Gostick, B. J. Hill, C. A. Hage, Z. Brahmi, A. Khoruts, H. L. Twigg, T. W. Schacker, D. C. Douek

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalMucosal Immunology
Volume1
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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