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*
Unité de Recherche Associée 1461, Centre National de la Recherche Scientifique,
Pathology Department, and
Institut National de la Santé et de la Recherche Médicale, Unité 429, Hopital Necker-Enfants Malades, Faculté Necker, Université Paris-V René-Descartes, Paris, France; and
§
Institut National de la Santé et de la Recherche Médicale, Contrat Jeune Formation 95–01, Institut Curie, Section Recherche, Paris, France
TGF-ß1 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-ß1 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-
and IL-1, TGF-ß1 prevents the final LC maturation in
response to TNF-, 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-ß1. 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-ß1, inflammatory stimuli may not be sufficient to induce full maturation of LC, thus avoiding potentially harmful immune responses. We conclude that TGF-ß1 appears to be responsible for both the acquisition of LC phenotype, cytokine production pattern, and prevention of noncognate maturation.
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F. Geissmann, Y. Lepelletier, S. Fraitag, J. Valladeau, C. Bodemer, M. Debre, M. Leborgne, S. Saeland, and N. Brousse Differentiation of Langerhans cells in Langerhans cell histiocytosis Blood, March 1, 2001; 97(5): 1241 - 1248. [Abstract] [Full Text] [PDF]
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H. A. Anderson, D. T. Bergstralh, T. Kawamura, A. Blauvelt, and P. A. Roche Phosphorylation of the Invariant Chain by Protein Kinase C Regulates MHC Class II Trafficking to Antigen-Processing Compartments J. Immunol., November 15, 1999; 163(10): 5435 - 5443. [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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