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CUTTING EDGE |
-Dependent Manner1Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
Dendritic cells (DCs) play a critical role in both initiating immune responses and in maintaining peripheral tolerance. However, the exact mechanism by which DCs instruct/influence the generation of effector vs regulatory T cells is not clear. In this study, we present evidence that TGF-
, an important immunoregulatory molecule, is present on the surface of ex vivo immature human DCs bound by latency-associated peptide (LAP). Maturation of DCs upon stimulation with LPS results in loss of membrane-bound LAP and up-regulation of HLA class II and costimulatory molecules. The presence of LAP on immature DCs selectively inhibits Th1 cell but not Th17 cell differentiation and is required for differentiation and/or survival of Foxp3-positive regulatory T cells. Taken together, our results indicate that surface expression of TGF- on DCs in association with LAP is one of the mechanisms by which immature DCs limit T cell activation and thus prevent autoimmune responses.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant NS23132.
2 Address correspondence and reprint requests to Dr. Howard L. Weiner, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115. E-mail address: hweiner{at}rics.bwh.harvard.edu
3 Abbreviations used in this paper: DC, dendritic cell; LAP, latency-associated peptide; mDC, myeloid DC; pDC, plasmacytoid DC; Treg, regulatory T cell; siRNA, small interfering RNA; int, intermediate.
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