1,25-Dihydroxyvitamin D3 acts directly on human lymphocytes and interferes with the cellular response to...

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) inhibits mitogen-induced lymphocyte proliferation in peripheral blood mononuclear cell preparations. Receptors for 1,25(OH)2D3 are present in monocytes and are acquired by lymphocytes upon activation. It is not clear whether the hormone inhibits lymphocyte mitogenesis by a direct action on the lymphocyte or only indirectly by affecting the regulatory monocytes. We addressed this question by using highly purified human lymphocyte preparations which contain less than 0.1% monocytes. 1,25(OH)2D3 inhibited the stimulation of purified lymphocytes by phytohemagglutinin and in the presence of fixed accessory cells, which cannot respond to 1,25(OH)2D3. The inhibitory effect attained 35% similar to that obtained in the presence of monocytes. 1,25(OH)2D3 inhibited interleukin 2 (IL-2)-driven stimulation of purified T cells in three different systems: cells treated with a submitogenic concentration of phytohemagglutinin, IL-2-dependent cells which bear receptors for IL-2 and naive cells in the absence of other mitogens. We conclude: (1) the human T lymphocyte is a direct target for 1,25(OH)2D3; (2) 1,25(OH)2D3 inhibits the response of activated, IL-2-receptor-bearing human T cells to interleukin-2.