1,25-Dihydroxyvitamin D3 (calcitriol) suppresses concanavalin A-stimulated human T cell proliferation through monocytes.
1,25-Dihydroxyvitamin D3 (calcitriol) inhibits mitogen-stimulated T cell proliferation by blocking the production of interleukin 2 (IL-2). The present study was initiated to determine the role of monocytes (Mo) in this process. Either Mo or T cells were preincubated with calcitriol for 24 or 48 hr and were thoroughly washed prior to concanavalin A (Con A)-stimulated coculture period. The inhibitory effect of calcitriol was Mo mediated; pretreatment of Mo resulted in inhibition of T cell proliferation, whereas pretreatment of T cells lacked the suppressive effect. Similar results were obtained by using 7- to 20-day-old IL-2-dependent human cultured T cells instead of fresh T cells. Calcitriol did not diminish the IL-1 secretion or intracellular IL-1 production of fresh Mo and actually increased the secretion of 24-hr-old Mo. Furthermore, addition of recombinant IL-1 to Mo-T cell coculture failed to reconstitute proliferative defect. Thus, these experiments clearly demonstrate that the suppression of Con A-driven T cell proliferation by calcitriol is Mo mediated and works by a non-IL-1 mechanism. At least, under these experimental conditions of Con A-driven T cell proliferation in which Mo play an obligatory role, antiproliferative action of calcitriol is Mo dependent.
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Department of Medicine, Veterans Administration Medical Center, East Orange, New Jersey 07019.
D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D003208:Concanavalin A; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011994:Recombinant Proteins; D003208:Concanavalin A; D002117:Calcitriol