Human plasmacytoid dendritic cells sequentially up-regulate and co-express functional receptors and IFN-α in response to HIV and HSV stimulation. (105.18)

Abstract Human plasmacytoid dendritic cells undergo functional and phenotypic changes upon viral stimulation. These changes lead to IFN-α production and a coordinated modulation of functional receptors and cytokine production crucial for antigen presentation, T cell activation and trafficking. We investigated whether the same pDC that produce IFN-α express receptors involved in antigen presentation or whether these are functions of distinct subsets. Using flow cytometry and SPICE® analysis, we observed not only time- and stimulus-dependent activation profiles in these activated pDC, but also their ability to concurrently express multiple receptors important for their function as APCs on HIV-1 and HSV-1 stimulation. Kinetics of pDC activation were slightly slower with HIV than with HSV stimulation. CDs 40, 80, 83, 86, PD-L1, MHCII, CCR5 and CCR7 were up-regulated concurrently with IFN-α and TNF-α in a pDC subpopulation, CXCR4 was recycled and CD62L was shed in this same subpopulation. We found subpopulations of pDC that expressed IFN-α and activation markers either singly or together. From the phenotypic progress over time, we hypothesize that these represent pDC that start producing IFN-α, then co-express IFN/activation markers, then go on to become fully mature. Further studies will tease apart interactions between these subsets and other cells of the immune system, especially in disease manifestations like HIV that specialize in suppressing and altering pDC function and phenotype.