Journal
MUCOSAL IMMUNOLOGY
Volume 1, Issue 1, Pages 49-58Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2007.5
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Funding
- Medical Research Council (UK)
- NIH [K08HL04545-05, R01 HL083468, R01HL59834, R01 AI54232, K24 AI056986, R01 DE-12934]
- NIAID
- MRC [G0501963] Funding Source: UKRI
- Medical Research Council [G0501963] Funding Source: researchfish
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL004545, R01HL083468, R01HL059834] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005066, R01AI054232, R56AI054232, K24AI056986, ZIAAI001029] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE012934] Funding Source: NIH RePORTER
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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.
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