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Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2002, Vol. 99, No. 7, pp. 2468-2476 IMMUNOBIOLOGY CD4+ and CD8+ anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity Kerstin Steinbrink, Edith Graulich, Sebastian Kubsch, Jürgen Knop, and Alexander H. Enk From the Department of Dermatology, University of Mainz, Germany. Interleukin-10 (IL-10)-treated dendritic cells (DCs) induce an alloantigen- or peptide-specific anergy in various CD4+ and CD8+ T-cell populations. In the present study, we analyzed whether these anergic T cells are able to regulate antigen-specific immunity. Coculture experiments revealed that alloantigen-specific anergic CD4+ and CD8+ T cells suppressed proliferation of syngeneic T cells in a dose-dependent manner. The same effect was observed when the hemagglutinin-specific CD4+ T-cell clone HA1.7 or tyrosinase-specific CD8+ T cells were cocultured with anergic T cells of the same specificity. Anergic T cells did not induce an antigen-independent bystander inhibition. Suppression was dependent on cell-to-cell contact between anergic and responder T cells, required activation by antigen-loaded DCs, and was not mediated by supernatants of anergic T cells. Furthermore, anergic T cells displayed an increased extracellular and intracellular expression of cytotoxic T-lymphocye antigen (CTLA)-4 molecules, and blocking of the CTLA-4 pathway restored the T-cell proliferation up to 70%, indicating an important role of the CTLA-4 molecule in the suppressor activity of anergic T cells. Taken together, our experiments demonstrate that anergic T cells induced by IL-10-treated DCs are able to suppress activation and function of T cells in an antigen-specific manner. Induction of anergic T cells might be exploited therapeutically for suppression of cellular immune responses in allergic or autoimmune diseases with identified (auto) antigens. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Chamorro, J. J. Garcia-Vallejo, W. W. J. Unger, R. J. Fernandes, S. C. M. Bruijns, S. Laban, B. O. Roep, B. A. 't Hart, and Y. van Kooyk TLR Triggering on Tolerogenic Dendritic Cells Results in TLR2 Up-Regulation and a Reduced Proinflammatory Immune Program J. Immunol., September 1, 2009; 183(5): 2984 - 2994. [Abstract] [Full Text] [PDF] F. Zhao, C. Falk, W. Osen, M. Kato, D. Schadendorf, and V. Umansky Activation of p38 Mitogen-Activated Protein Kinase Drives Dendritic Cells to Become Tolerogenic in Ret Transgenic Mice Spontaneously Developing Melanoma Clin. Cancer Res., July 1, 2009; 15(13): 4382 - 4390. 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