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.
Medical Department TTA, Rigshospitalet State University Hospital, Copenhagen, Denmark.
K
K
Müller
N
N
Odum
K
K
Bendtzen
D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D007376:Interleukin-2; D002117:Calcitriol