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

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 HIVspecific 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 Tcell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells.

HIV-1 Infection Impairs the Bronchoalveolar T-Cell Response to Mycobacteria

“…Another study found no depletion of CCR5 1 memory CD4 T cells in BAL from HIV-1-infected persons, compared with healthy controls (29). These authors argued that quantification of total CD4 cells is confounded by the inverted CD4/CD8 ratios at mucosal sites, such as the gut, compared with blood.…”

“…Additional conscious sedation with intravenous midazolam was given at the discretion of the operator. Standard flexible diagnostic bronchoscopy was performed, including a BAL of the middle lobe with 300 ml sterile saline instilled in 50-ml volumes as previously described (29). BAL fluid was stored on ice for a maximum of 30 minutes until bronchoalveolar lavage mononuclear cells (BALMC) were prepared as previously described (19), washed with phosphate-buffered saline, and strained through a 100-mm filter (Partec CellTrics; Partec Co., Mü nster, Germany).…”

“…Bronchoalveolar HIV-1-specific CD4 cells have been shown to be more polyfunctional, coexpressing IFN-g, IL-2, and TNF-a, than peripheral HIV-1-specific CD4 cells (29). We compared the functionality of PPD-and BCG-specific CD4 T cells in these two compartments.…”

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…First and foremost, it is possible that a different "quality" of CD4 ϩ T-cell depletion in natural versus nonnatural SIV hosts at the intestinal mucosal level plays a major role. Indeed, both SIV-infected RM and HIV-infected persons experience a significant and preferential reduction of the IL-17-producing CD4 ϩ (Th17) and CD8 ϩ (Tc17) T-cell subsets throughout the gastrointestinal tract (81)(82)(83)(84). Similarly, the depletion of IL-17-producing innate lymphocytes in the GI tracts of SIV-infected Asian macaques has been demonstrated (85,86).…”

HIV-Associated Lung Infections and Complications in the Era of Combination Antiretroviral Therapy

“…The mucosal depletion of gut CD4 1 T cells does not appear to occur within the lung. In contrast, bronchoalveolar lavage (BAL) fluid from HIVinfected individuals early in infection has demonstrated higher numbers of CD4 1 T cells, which were also more polyfunctional, when compared with the terminal ileum (11). HIV-infected individuals, particularly in early-to mid-stage disease, have increased numbers of HIV-specific cytotoxic CD8 1 T lymphocytes within the alveolar space (12).…”