1,25-Dihydroxyvitamin D3 (calcitriol) suppresses concanavalin A-stimulated human T cell proliferation through...

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.