Inhibitory effect of cyclosporin A on antigen and alloantigen presenting capacity of human epidermal Langerhans cells.
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 cytotoxic 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 RFD1 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.
Teunissen
M B
MB
Department of Dermatology, University of Amsterdam, The Netherlands.
De Jager
M H
MH
Kapsenberg
M L
ML
Bos
J D
JD
D000938:Antigen-Presenting Cells / Q000187:drug effects*; D001681:Biological Assay; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
D007375:Interleukin-1; D011458:Prostaglandins E; D016572:Cyclosporine