Physiological concentrations of transforming growth factor β1 selectively inhibit human dendritic cell function

In this study the effects of different in vitro conditioning with transforming growth factor (TGF) β1 on human monocyte-derived DC maturation (hMo-DC) were investigated. hMo-DC differentiated in the presence of physiologically relevant concentrations of TGFβ1 (2 ng/ml) failed to undergo complete maturation despite adequate stimulation with LPS or LPS + IFNγ.These hMo-DC did not produce IL-12p70 or PGE2, and showed decreased IL-10 and IL-18 production and HLA-DR expression. However, the expression of these molecules, except for IL-12p70, was not significantly affected in hMo-DC differentiated in the presence of lower concentrations of TGFβ1 (0.2 and 0.02 ng/ml). Exposure of hMo-DC to TGFβ1 (2 ng/ml) after they had completed differentiation had minimal effects. Thus, the functional response of hMo-DC to LPS or LPS + IFNγ depended on the stage of hMo-DC differentiation at which cells were first exposed to TGFβ1 and on the concentration of TGFβ1. These results suggest that in the in vivo micro-environment, the concentrations and the timing of monocyte exposure to TGFβ1 may be crucial in the differentiation of DC toward more or less mature phenotypes, and this may have important implications for DC functions. The decrease in T-cell proliferation and a small increase in IL-5 production by T cells co-cultured with hMo-DC that had been treated with TGFβ1, suggest the possibility that in vivo such DC may provide chronic, but incomplete signals to T cells, and this could be a potential mechanism underlying polarisation of T cells towards anergy.