Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines

Abstract

Local activation of T lymphocytes is regarded as an important immunological component of psoriatic skin lesions. Within psoriatic plaques (PP) there are large numbers of dermal dendritic cells (DDCs) immediately beneath the hyperplastic epidermis surrounded by T cells. In this study we investigated the ability of DDCs isolated from PP skin to support immune responses to resting peripheral blood T cells. For comparison, other dendritic cells were obtained from blood of the same psoriatic patients, as well as DDCs from skin of normal healthy individuals (designated NN skin). All dendritic cells studied had high surface expression of HLA-DR, B7, and lymphocyte function associated antigen-1 molecules. T cell proliferative responses and cytokine production profiles to these various dendritic cells were measured in the absence and presence of PHA or bacterial-derived superantigens. In the absence of exogenous mitogens, PP skin-derived DDCs were much more effective stimulators of spontaneous T cell proliferation compared with either psoriatic blood-derived or NN skin-derived dendritic cells. Antibody blocking studies revealed involvement of HLA-DR, B7, and lymphocyte function associated antigen-1 on PP skin-derived DDCs. Cytokine profiles revealed that in the absence of exogenous stimuli PP skin-derived DDCs mediated a T cell response with high levels of IL-2 and IFN-gamma, but not IL-4 or IL-10. NN skin-derived DDCs produced a similar qualitative response, but quantitative amounts of all cytokines measured were lower. Upon addition of PHA or superantigens, both PP skin-derived and NN skin-derived DDCs mediated high levels of IL-2 and IFN-gamma production, with induction of IL-4 particularly evident for PHA reactions. Addition of conditioned medium from psoriatic dermal fragments did not enhance the autostimulatory capacity of blood-derived dendritic cells. These findings highlight the potent autostimulatory potential of PP skin-derived DDCs and suggest an important immunological contribution for these previously overlooked cell types contained within lesional skin sites.