1,25-dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro
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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.
Original language | English |
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Journal | Immunology Letters |
Volume | 35 |
Issue number | 2 |
Pages (from-to) | 177-82 |
Number of pages | 5 |
ISSN | 0165-2478 |
DOIs | |
Publication status | Published - 1993 |
Bibliographical note
Keywords: Antibodies; Antibodies, Monoclonal; Antigens, CD; Antigens, CD28; Antigens, CD3; Antigens, CD4; Antigens, Differentiation, T-Lymphocyte; Calcitriol; Cell Division; Cell Line; Dose-Response Relationship, Drug; Humans; Interleukin-2; T-Lymphocytes
ID: 10636149