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Background:   Dendritic cells (DC) are components of the innate immune system that are key regulators of adaptive immunity. There are 2 main subsets of circulating DC (DC1 [myeloid] and DC2), both of which are depleted in progressive HIV infection, and which recover variably following HAART. The recovery of DC2 populations has been demonstrated to be at least as important as that of CD4⁺ T cells in protection from opportunistic infections. However, information is limited regarding timing of initiation of HAART on DC subsets, and their relationship to T-cell function. We performed a cross-sectional in vitro investigation to evaluate DC number and function and T-cell immunity in groups of patients who had initiated HAART at high and low CD4⁺ T-cell nadirs.

Methods:  Flow cytometry was employed to enumerate DC subsets and assess their function by intracellular TNF-a expression following stimulation with resiquimod. CD4⁺ T-cell responses to HIV, CMV, and Candida antigens were evaluated by lymphocyte proliferation assay; CD8⁺ T-cell responses were evaluated by IFN-g ELISpot, following stimulation with recombinant vaccinia expressing CMV and HIV genes.

Results: “High” (n = 19) and “low” (n = 17) nadir subjects had documented CD4⁺ T-cell nadirs of 436 ± 39 and 23 ± 5 cells/mm³, respectively. All patients had received HAART for > 12 months and had current plasma vRNA < 200 copies/mL and CD4⁺ T-cell counts > 350 cells/mm³. We observed no differences in numbers or function of DC subsets or in HIV-specific or anti-microbial CD4⁺ or CD8⁺ T-cell responses between the groups. There was, however, a significant positive correlation between DC2 number and function and CD4:CD8 T-cell ratio (R = 0.66, p < 0.0001 and R = 0.49, p = 0.0065, respectively).  Furthermore, there was a significant negative correlation between numbers of DC2 cells and expression on CD8⁺ T cells of the activation markers CD38 and HLA-DR (R = –0.39, p = 0.035 and R = –0.46, p = 0.01, respectively). There were no significant relationships between DC1 and T cell parameters.

Conclusions:  The timing of HAART has no apparent effect on either recovery of DC subsets or on HIV-, CMV-, or Candida-specific T-cell function. Our data suggest an immune regulatory role of the DC2 subset in limiting pathologic CD8⁺ T-cell activation and facilitating normalization of the CD4⁺:CD8⁺ T-cell ratio.

Keywords: Dendritic cells ; CD4+ cells; CD8+ cells