TGF-β1 Prevents the Noncognate Maturation of Human Dendritic Langerhans Cells

作者：Frédéric Geissmann, Patrick Revy, Armelle Régnault, Yves Lepelletier, Michel Dy, Nicole Brousse, Sebastián Amigorena, Olivier Hermine, Anne Durandy · 发表于：The Journal of Immunology · 年份：1999 · DOI：10.4049/jimmunol.162.8.4567 · 被引用次数：330 · 研究领域：Immunotherapy and Immune Responses、T-cell and B-cell Immunology、vaccines and immunoinformatics approaches

Abstract TGF-β1 is critical for differentiation of epithelial-associated dendritic Langerhans cells (LC). In accordance with the characteristics of in vivo LC, we show that LC obtained from human monocytes in vitro in the presence of TGF-β1 1) express almost exclusively intracellular class II Ags, low CD80, and no CD83 and CD86 Ags and 2) down-regulate TNF-RI (p55) and do not produce IL-10 after stimulation, in contrast to dermal dendritic cells and monocyte-derived dendritic cells. Surprisingly, while LC exhibit E-cadherin down-regulation upon exposure to TNF-α and IL-1, TGF-β1 prevents the final LC maturation in response to TNF-α, IL-1, and LPS with respect to Class II CD80, CD86, and CD83 Ag expression, loss of FITC-dextran uptake, production of IL-12, and Ag presentation. In sharp contrast, CD40 ligand cognate signal induces full maturation of LC and is not inhibited by TGF-β1. The presence of emigrated immature LCs in human reactive skin-draining lymph nodes provides in vivo evidence that LC migration and final maturation may be differentially regulated. Therefore, due to the effects of TGF-β1, inflammatory stimuli may not be sufficient to induce full maturation of LC, thus avoiding potentially harmful immune responses. We conclude that TGF-β1 appears to be responsible for both the acquisition of LC phenotype, cytokine production pattern, and prevention of noncognate maturation.