Modulation of T-lymphocyte proliferation by exogenous natural ceramides and sphingosylphosphorylcholine

Sphingolipids such as ceramide and sphingosine are abundantly present in th e stratum corneum of epidermis. In atopic stratum corneum, sphingosylphosph orylcholine (SPC) is present in association with a reduction in the amount of ceramides. We have previously shown that the cellular kinetics of T cell s are affected by exogenous addition of sphingosine and synthetic ceramides , raising the possibility that sphingolipids diffusing from the stratum cor neum modulate skin-infiltrating T cells. By using two natural ceramides and murine T cells, this study further clarified the conditions under which ex ogenous ceramides enhance the proliferation of T cells. KLH-specific T cell clones 28-4 and 24-2 proliferated in response to natural ceramides when cu ltured for 44-48 h in the presence of concanavalin A at 1 mu g per ml. Elon gation of culture periods adversely inhibited the T cell proliferation, sug gesting the existence of an optimal exposure time. Augmentation of DNA synt hesis by natural ceramides was more pronounced in tumor necrosis factor alp ha (TNF alpha)-sensitive 28-4 cells than in less sensitive 24-2 cells, and TNF alpha-induced proliferation of 28-4 cells was suppressed by the concomi tant addition of natural ceramides. Similar to ceramides, SPC augmented the proliferation of resting spleen cells. Our study suggests that ceramide mo dulation of T cell proliferation depends on the TNF alpha sensitivity and a ctivation level of T cells and that SPC also has a mitogenic potential for T cells.