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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1162-1169. Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-03-1211. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1211v1 105/3/1162    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Levings, M. K. Articles by Roncarolo, M. G. Search for Related Content PubMed PubMed Citation Articles by Levings, M. K. Articles by Roncarolo, M. G. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells Megan K. Levings, Silvia Gregori, Eleonora Tresoldi, Sabrina Cazzaniga, Chiara Bonini, and Maria Grazia Roncarolo From the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET); Cancer Immunotherapy and Gene Therapy Program, San Raffaele Scientific Institute; and Università Vita-Salute San Raffaele Milan, Italy. Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the antigenic environment and activate naive T cells. The role of DCs is not only to sense danger but also to tolerize the immune system to antigens encountered in the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell encounters its antigen on immature DCs (iDCs), it may differentiate into a T-regulatory (Tr) rather than a T-effector cell. However, little is known about the mechanisms by which iDCs differentiate Tr cells. We developed a standardized and highly reproducible protocol to differentiate Tr cells by repetitive exposure of naive peripheral blood CD4+ T cells to allogeneic iDCs. The resultant Tr cells are phenotypically and functionally identical to type 1 Tr (Tr1) cells because their generation requires production of IL-10 by iDCs, and they suppress T-cell responses through an interleukin-10 (IL-10)– and a transforming growth factor (TGF-)–dependent mechanism. In addition, Tr1 cells induced by iDCs do not require the presence of CD4+CD25+ Tr cells for their generation, nor do they express high constitutive levels of CD25 or the transcription factor FoxP3. Thus, iDCs can drive the differentiation of Tr1 cells and can be used to generate large numbers of alloantigen-specific Tr1 cells for clinical use as a cellular therapy to restore peripheral tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Girard, E. Israel-Assayag, and Y. Cormier Mature CD11c+ cells are enhanced in hypersensitivity pneumonitis Eur. Respir. J., September 1, 2009; 34(3): 749 - 756. [Abstract] [Full Text] [PDF] L. Gabrysova, K. S. Nicolson, H. B. Streeter, J. Verhagen, C. A. Sabatos-Peyton, D. J. Morgan, and D. C. Wraith Negative feedback control of the autoimmune response through antigen-induced differentiation of IL-10-secreting Th1 cells J. Exp. Med., August 3, 2009; 206(8): 1755 - 1767. [Abstract] [Full Text] [PDF] C. Luther, E. Adamopoulou, C. Stoeckle, V. Brucklacher-Waldert, D. Rosenkranz, L. Stoltze, S. Lauer, S. Poeschel, A. Melms, and E. 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