Background: Dendritic cell (DC) subsets are associated with activation and function of innate and adoptive immune responses. Using a panel of new DC markers identifying CD11c+ myeloid (MDC) and IFN-alpha-secreting plasmacytoid DC (PDC) subsets, we quantified and assessed the functional properties of these 2 major DC subsets in a cross-sectional study in a cohort of 65 HIV-infected subjects and 57 uninfected controls.
Differential Depletion and Reconstitution on Therapy of the Dendritic Cell Repertoire in Circulating Blood of HIV+ Individuals|
J. Chehimi1, D. Campbell2, L. Azzoni1, D. Bacheller2, G. Jerandi1, S. Black3, K. Mounzer3, J. Shull3, J. Kostman3,4, and L. J. Montaner*1
1Wistar Inst.; 2Children's Hosp.; 3Philadelphia FIGHT; and 4Univ. of Pennsylvania, Philadelphia
Methods: Consenting controls and HIV+ individuals at various stage of the disease were enrolled in this study. Whole blood 3/4-color staining was performed with the following antibodies: HLA-DR, Lin cocktail, CD123, CD11c, BDCA2, and BDCA3. Functional analysis was performed by testing the IFN-alpha production after stimulation with Flu or HSV, and by MLR using non-adherent umbilical cord blood cells as responders.
Results: We show a significant decrease of Lin-/HLA-DR+/CD123+, Lin-/HLA-DR+/BDCA2+ PDC in patients as compared to uninfected controls (p<0.0001). Loss of the PDC subsets was observed independent of suppressive HAART, CD4 count, or viral load suggesting an irreversible change after infection. This decrease was also associated with an impairment of Flu- and HSV-induced IFN-alpha production by HIV-infected subjects as compared to uninfected controls (p<0.0001). In contrast, Lin-/HLA-DR+/CD11c+ and associated MLR were not significantly different to uninfected controls although a significant decrease was found in patients with a viral load of >5000 copies/mL. Analysis of BDCA3+ subsets showed a pattern of changes resembling CD123+ PDC rather than the CD11c+ MDC subset. Only CD11c+ MDC subset was inversely associated with viral load (rho=-0.5, p<0.0001, n=65); this was confirmed confirmed in a subset of patients not on therapy (n=21), suggesting a greater role for CD11c MDC in viral control.
Conclusions: Our data indicated a lack of immune reconstitution in the depleted PDC repertoire in suppressed patients on HAART. Importantly, MDC subset is increased in patients on therapy at <5000 copies/mL and is inversely associated with viral replication, indicating a potential contribution of this subset in viral control.