Although the precise mechanism of action of cyclosporine (CS) is unknown, there is substantial evidence that CS preferentially acts on T cells by impairing lymphokine production. Recent studies have demonstrated that CS may also inhibit the functions of accessory cells and APC. Since topically applied CS inhibits contact sensitivity and epidermal Langerhans cells (LC) are very effective accessory cells and APC, we determined whether CS directly affects their accessory cell functions. Murine LC were pulsed with solvent control or with various doses of CS (up to 10 micrograms/ml) and then Con A-induced T cell proliferation was assayed. CS pulsing of LC caused, when compared with solvent control-pulsed LC, a dose-dependent decrease in T cell stimulation (up to 93%). LC fixed with paraformaldehyde after 2-h CS pulsing showed a similar degree of decreased accessory cell function, indicating that the immunosuppressive action is established by 2 h. The inhibitory capacity of CS pulsing on LC is not likely to be related to diminished IL-1 production, enhanced PG biosynthesis, or decreased surface Ia Ag intensity. The possibility of carryover of CS into the culture supernatants was ruled out by adding CS-pulsed LC or their supernatants to other T cell proliferative assays. Thus, these studies indicate that CS directly inhibits accessory cell functions of LC.

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