TY - JOUR

T1 - 1,25-dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro

AU - Müller, K

AU - Odum, Niels

AU - Bendtzen, K

N1 - 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

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

U2 - 10.1016/0165-2478(93)90088-J

DO - 10.1016/0165-2478(93)90088-J

M3 - Journal article

C2 - 8389732

VL - 35

SP - 177

EP - 182

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

IS - 2

ER -