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,
*
Laboratory of Experimental Surgery, Surgical Department, and
Department of Pathology, San Raffaele Scientific Institute, Milan, Italy;
University of Milan, Milan, Italy;
§
Department of Immunology and Cell Biology, Mario Negri Institute, Milan, Italy
We studied the effects of 1
,25-dihydroxyvitamin D3
(1,25-(OH)2D3) on differentiation,
maturation, and functions of dendritic cells (DC) differentiated from
human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days.
Recovery and morphology were not affected by
1,25-(OH)2D3 up to 100 nM. DC differentiated
in the presence of 10 nM 1,25-(OH)2D3
(D3-DC) showed a marked decrease in the expression of CD1a,
while CD14 remained elevated. Mannose receptor and CD32 were
significantly increased, and this correlated with an enhancement of
endocytic activity. Costimulatory molecules such as CD40 and CD86 were
slightly decreased or nonsignificantly affected (CD80 and MHC II).
However, after induction of DC maturation with LPS or incubation with
CD40 ligand-transfected cells, D3-DC showed marginal
increases in MHC I, MHC II, CD80, CD86, CD40, and CD83. The accessory
cell function of D3-DC in classical MLR was also inhibited.
Moreover, allogeneic T cells stimulated with D3-DC were
poor responders in a second MLR to untreated DC from the same or an
unrelated donor, thus indicating the onset of a nonspecific
hyporesponsivity. In conclusion, our data suggest that
1,25-(OH)2D3 may modulate the immune system,
acting at the very first step of the immune response through the
inhibition of DC differentiation and maturation into potent
APC.
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T. P. Staeva-Vieira and L. P. Freedman 1,25-Dihydroxyvitamin D3 Inhibits IFN-{gamma} and IL-4 Levels During In Vitro Polarization of Primary Murine CD4+ T Cells J. Immunol., February 1, 2002; 168(3): 1181 - 1189. [Abstract] [Full Text] [PDF]
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A. Boonstra, F. J. Barrat, C. Crain, V. L. Heath, H. F. J. Savelkoul, and A. O'Garra 1{alpha},25-Dihydroxyvitamin D3 Has a Direct Effect on Naive CD4+ T Cells to Enhance the Development of Th2 Cells J. Immunol., November 1, 2001; 167(9): 4974 - 4980. [Abstract] [Full Text] [PDF]
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S. Gregori, M. Casorati, S. Amuchastegui, S. Smiroldo, A. M. Davalli, and L. Adorini Regulatory T Cells Induced by 1{alpha},25-Dihydroxyvitamin D3 and Mycophenolate Mofetil Treatment Mediate Transplantation Tolerance J. Immunol., August 15, 2001; 167(4): 1945 - 1953. [Abstract] [Full Text] [PDF]
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H. Hackstein, A. E. Morelli, A. T. Larregina, R. W. Ganster, G. D. Papworth, A. J. Logar, S. C. Watkins, L. D. Falo, and A. W. Thomson Aspirin Inhibits In Vitro Maturation and In Vivo Immunostimulatory Function of Murine Myeloid Dendritic Cells J. Immunol., June 15, 2001; 166(12): 7053 - 7062. [Abstract] [Full Text] [PDF]
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M. D. Griffin, W. Lutz, V. A. Phan, L. A. Bachman, D. J. McKean, and R. Kumar Dendritic cell modulation by 1alpha ,25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo PNAS, June 5, 2001; 98(12): 6800 - 6805. [Abstract] [Full Text] [PDF]
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