Physiological concentrations of transforming growth factor beta1 selectively inhibit human dendritic cell function.
In this study the effects of different in vitro conditioning with transforming growth factor (TGF) beta1 on human monocyte-derived DC maturation (hMo-DC) were investigated. hMo-DC differentiated in the presence of physiologically relevant concentrations of TGFbeta1 (2 ng/ml) failed to undergo complete maturation despite adequate stimulation with LPS or LPS+IFNgamma. 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 TGFbeta1 (0.2 and 0.02 ng/ml). Exposure of hMo-DC to TGFbeta1 (2 ng/ml) after they had completed differentiation had minimal effects. Thus, the functional response of hMo-DC to LPS or LPS+IFNgamma depended on the stage of hMo-DC differentiation at which cells were first exposed to TGFbeta1 and on the concentration of TGFbeta1. These results suggest that in the in vivo micro-environment, the concentrations and the timing of monocyte exposure to TGFbeta1 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 TGFbeta1, 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.
Lung Institute of Western Australia and Centre for Asthma, Allergy & Respiratory Research, The University of Western Australia, Perth, WA, Australia. mirjanaf@aari.uwa.edu.au
Mirjana
M
Fogel-Petrovic
Julie A
JA
Long
Neil L
NL
Misso
Paul S
PS
Foster
Kanti D
KD
Bhoola
Philip J
PJ
Thompson
D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D045142:Cross-Priming / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D017634:Self Tolerance / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma