Studies on the immunosuppressive properties of 7,25 dihydroxycholesterol--II. Effects on early steps of T-cell activation.

The effects of an oxysterol, 7,25-dihydroxycholesterol (7,25-OHC), cyclosporin A (CsA) and dexamethasone (Dex) on the blastogenic response of murine lymphocytes to various stimuli were investigated. 7,25-OHC markedly depressed the response to Con A, anti-T3 monoclonal antibodies and to the combination phorbol myristate acetate (PMA) + IL-2 and PMA + ionomycin. Dexamethasone was also active within the same range of concentrations. However, it did not inhibit the stimulation induced by PMA + ionomycin. On the other hand, Cs A failed to depress the lymphocyte response to IL-2 + PMA. Therefore, the mechanisms of action involved in the blockage of lymphocyte activation are different for these three compounds. Moreover, we noted that 7,25-OHC was less active upon purified T-cells. Taken together, these results suggest that 7,25-OHC may act at the level of signal transduction across the membrane.