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.
Bibliographical noteFunding 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.