The role of monocytes and T cells in 1,25-dihydroxyvitamin D3 mediated inhibition of B cell function in vitro.
1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits immunoglobulin production by human mononuclear cells (MNC) in vitro. The present study was undertaken to evaluate the role of T cells and monocytes in 1,25-(OH)2D3 induced suppression of B cell functions. The synthetic vitamin D3 analogue MC 903 was examined in parallel. 1,25-(OH)2D3 and MC 903 showed a dose-related inhibition of IgM, IgG and IgA plaque-forming cells in poke-weed mitogen (PWM) activated cultures of MNC. This effect was most likely mediated through impairment of T cell and monocyte functions. First, the inhibitory effect was seen after PWM stimulation, but not after Epstein-Barr virus stimulation which activates B cells independently of T cells and monocytes. Second, 1,25-(OH)2D3 was not effective in T cell and monocyte-depleted cultures. Third, the effect of 1,25-(OH)2D3 on PWM driven MNC was reversed by addition of the recombinant monokines: interleukin (IL)-1 beta, tumour necrosis factor alpha (rTNF alpha), rIL-6, as well as the lymphokines: lymphotoxin (rLT) and rIL-2. This is consistent with the finding that 1,25-(OH)2D3 also inhibited IL-1 alpha, TNF alpha and LT production in these cultures. The assumption that B cells are not directly affected by 1,25-(OH)2D3 was further supported by the fact that 24 h of culture with 10(-8) M 1,25-(OH)2D3 failed to reduce immunoglobulin production by in vivo activated B cells.
Müller
K
K
Medical Department TTA, Rigshospitalet State University Hospital, Copenhagen, Denmark.
Heilmann
C
C
Poulsen
L K
LK
Barington
T
T
Bendtzen
K
K
D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002450:Cell Communication; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C055085:calcipotriene; D002117:Calcitriol