1,25-dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits the proliferation of mitogen-stimulated human mononuclear cells (MNC) as well as the production of a number of proinflammatory cytokines, including interleukin (IL)-1 alpha, IL-6, tumour necrosis factor-alpha, IL-2, interferon-gamma (IFNg) and lymphotoxin (LT). These effects are most likely mediated via specific vitamin D receptors expressed by monocytes and activated T lymphocytes. In the present study we have evaluated the ability of 1,25-(OH)2D3 to affect proliferation and cytokine production by human T cell lines stimulated by anti-CD3 antibodies or anti-CD3 plus anti-CD28 antibodies. 1,25-(OH)2D3 selectively reduced the supernatant levels of IL-2, while the IFNg and LT levels were unaffected. This was followed by a time- and dose-dependent reduction in proliferation. Although the expression of high affinity IL-2 receptors (IL-2R) (p75) was unaffected, exogenously added IL-2 failed to restore proliferation. The study demonstrates that human T cell lines, in the absence of accessory cells, may be a direct target for 1,25-(OH)2D3, resulting in a specific reduction of IL-2 levels and inhibition of proliferation. The mechanism by which 1,25-(OH)2D3 inhibits proliferation most likely involves interference with activation signals at the IL-2R level or at a post IL-2R level.