Inhibitory effect of cyclosporin A on antigen and alloantigen presenting capacity of human epidermal Langerhans cells

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Abstract
Summary The effect of cyclosporin A (CyA) on the capacity of human epidermal Langerhans cells (LC) to stimulate allogeneic T cells or to present antigen to autologous T cells was investigated. Preparations of LC enriched by discontinuous density gradient centrifugation were pulsed for 2 or 16 h with graded doses (5–5000 ng/ml) of CyA prior to co-culture with T cells. Pretreatment of LC with CyA resulted in a dose-dependent decrease of the functional capacity of LC to stimulate T cells. This inhibition (up to 90%). already achieved after a pulse of 2 h, was not due to a cytotoxie effect of the drug and appeared to be reversible. The possibility that CyA exerted its effect indirectly on T cells via release of CyA from LC into the supernatant during co-culture was excluded. The suppression of immunostimulatory function was a direct effect of the drug on LC. CyA did not affect the production by LC of IL-1 or prostaglandin nor the expression of MHC class II products HLA-D and RFDl or adhesion molecules ICAM-1 and LFA-3. These results suggest that inhibition of contact allergic skin reactions by CyA may be due in part to an impairment of the function of LC.