Suppression of in vitro cellular immune response by nitrogen-containing terpene alcohol derivatives

A series of nitrogen-containing terpene alcohol derivatives were tested for their immunosuppressive effects in vitro, and KYKC-407 (erythro-1-(1-imidazolyl)-3,7,11-trimethyl-dodecane-2(S),3(R)-diol) was found to be the most effective in suppressing the induction of cytotoxic T cell (CTL) activity. CTL induction in the coculture of C3H spleen cells with mitomycin C-treated BALB/c spleen cells was suppressed by more than 90% when 4 microM KYKC-407 was added to the culture. Under these conditions, lymphocyte proliferation was also suppressed to a similar extent by this compound. Flow cytometric analysis revealed that KYKC-407 strongly inhibited the proliferation of CD8+ T cell subset, but showed less suppressive effects on CD4+ T cells. In contrast to cyclosporin A, KYKC-407 at 1-4 microM did not inhibit the proliferative response to concanavalin A. Further, KYKC-407 suppressed CTL induction even in the presence of exogenous IL-2, thus suggesting that the compound does not exert its effects through inhibiting IL-2 production.