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

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

Research output: Contribution to journalArticlepeer-review

62 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
StatePublished - Jan 2008

Bibliographical note

Funding Information:
We thank Drs Rhame, Lifson, Kline, Simpson, Baker, Gupta, and Goldman for patient referral and the Indiana University GCRC for patient care. DAP is a Medical Research Council (UK) Senior Clinical Fellow. KSK is supported by NIH Grants K08HL04545-05 and R01 HL083468. HLT is supported by NIH Grant R01HL59834. TWS is supported by NIH Grants R01 AI54232, K24 AI056986, and R01 DE-12934. This work was supported, in part, by intramural funding from NIAID, NIH.

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