Inhibitory effect by 1,25-dihydroxyvitamin D3 on concanavalin A-stimulated proliferation of rat thymic lymphocytes

It has been reported that vitamin D3 derivatives promote the differentiation of monocytes into macrophages, while the derivatives suppress mitogen-stimulated proliferation of human peripheral blood-mononuclear cells (PBMC). However, their effect on thymic lymphocytes which are in the course of differentiation and maturation into T cells has not been thoroughly examined. The authors studied the inhibitory effect by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on concanavalin A (Con A)-stimulated proliferation of rat thymic lymphocytes and explored its mechanism. The proliferation of rat thymic lymphocytes stimulated with Con A was suppressed by 1,25-(OH)2D3 in a dose-dependent manner between a range of 10(-10) M to 10(-8) M. Because this suppressive action of 1,25-(OH)2D3 was markedly reduced by removal of coexisting adherent cells or by treatment with indomethacin which suppresses the prostaglandin E2 (PGE2) synthesis, it seems likely that PGE2, released from macrophages with the stimulation of 1,25-(OH)2D3, is involved in the suppressive action. Further studies on the inhibitory mechanism clarified that PGE2 from the contaminated macrophages suppressed the formation and release of interleukin-2 (IL-2), whereas the expression of IL-2 receptors on thymic lymphocyte with Con A stimulation was not affected. These results suggest that vitamin D3 derivatives might possibly contribute to regulation of in vitro proliferation of thymic lymphocytes.