Immunomodulatory Effects of 1,25-Dihydroxyvitamin D₃ on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Figure 6

1,25(OH)₂D₃-Treated DC induce stable antigen-specific T cell hyporesponsiveness to myelin-derived antigens (MOG/MBP peptides) in both healthy controls and MS patients. PBL stimulated with MOG/MBP peptides with or without autologous iDC or mDC were restimulated with MOG/MBP peptides (black bars) after 7 days of initial coculture. Controls represent nonrestimulated PBL (open bars). The secretion of IFN-γ was used as a measure for autologous T cell-stimulatory capacity. Each condition was measured in quadruple. Results are expressed as mean ± SEM. T cell hyporesponsiveness induced by 1,25(OH)₂D₃-treated DC of healthy controls () and MS patients () is shown, respectively, in (a) and (b). The antigen specificity of T cell hyporesponsiveness induced by 1,25(OH)₂D₃-treated DC was determined for healthy controls (c) and MS patients (d). PBL stimulated with MOG/MBP peptides with or without autologous DC were restimulated with either MOG/MBP peptides (black bars) or CMV pp65 peptides (dashed bars) after 7 days of initial coculture. ((e) and (f)) Stability of T cell hyporesponsiveness induced by 1,25(OH)₂D₃-treated DC of healthy individuals (e) and MS patients (f). PBL stimulated with MOG/MBP peptides with or without autologous DC were restimulated either with MOG/MBP peptides (black bars) or with MOG/MBP peptides combined with fully mature conventional DC (blocked bars) after 7 days of initial coculture. iDC, immature DC; cc-mDC, cytokine cocktail-matured DC; LPS-mDC, lipopolysaccharide-matured DC; PBL, peripheral blood lymphocytes; MOG, myelin oligodendrocyte glycoprotein; MBP, myelin basic protein; CMV, cytomegalovirus; and SFC, spot forming cells.