1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation.
The proliferative response of murine spleen and thymus cells to antigen but not to lectin was inhibited by the active metabolite of vitamin D3, 1,25-(OH)2D3. To directly examine the effect of 1,25-(OH)2D3 on T cell activation in the absence of other complicating interactions, we utilized a panel of cloned Ia-restricted T cell hybridomas that secrete IL 2 on activation by cloned Ia-bearing stimulator cells (TA3) or when stimulated by mitogen. Physiologic concentrations of 1,25-(OH)2D3 (0.01 to 0.1 nm) inhibited the antigen-induced secretion of IL 2 by several of these T cell hybridomas. This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of Ia-bearing stimulator cells used. Pretreatment of the T hybridoma but not the TA3 stimulator cell with 1,25-(OH)2D3 resulted in inhibition of activation. These results are consistent with the finding that specific 1,25-(OH)2D3 receptors are present on the T cell hybridomas but are lacking in TA3 cells. 1,25-(OH)2D3 failed, however, to inhibit the activation of the T cell hybridomas by lectin or by an anti-Thy-1 antibody. These findings suggest that 1,25-(OH)2D3 may be interfering with early events of antigen-induced T cell activation, perhaps by hindering T cell recognition of the relevant antigen on stimulator cell surfaces. This system should prove useful in studying the molecular mechanisms by which 1,25-(OH)2D3 acts to inhibit T cell activation and subsequent IL 2 production.
D000818:Animals; D000941:Antigens / Q000276:immunology; D002117:Calcitriol / Q000494:pharmacology*; D000939:Epitopes; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D000939:Epitopes; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol