HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bruder, D. Articles by Buer, J. Search for Related Content PubMed PubMed Citation Articles by Bruder, D. Articles by Buer, J. Social Bookmarking                What's this?

On the Edge of Autoimmunity

T-Cell Stimulation by Steady-State Dendritic Cells Prevents Autoimmune Diabetes

¹ Department of Mucosal Immunity, German Research Centre for Biotechnology, Braunschweig, Germany
² Department of Veterinary Pathology, Free University Berlin, Berlin, Germany
³ Department of Dermatology, University of Heidelberg, Heidelberg, Germany
⁴ Dana Faber Cancer Institute, Harvard Medical School, Boston, Massachusetts
⁵ Institute of Medical Microbiology, Hannover Medical School, Hannover, Germany

Targeting of antigens to immature dendritic cells has been shown to result in antigen-specific T-cell tolerance in vivo. In the INS-HA/TCR-HA transgenic mouse model for type 1 diabetes, we tested the potential of the dendritic cell–specific monoclonal antibody DEC-205 conjugated to the hemagglutinin (HA) antigen (DEC-HA) to prevent disease onset. Whereas untreated INS-HA/TCR-HA mice all develop insulitis, and 40% of these mice become diabetic, repeated injection of newborn mice with DEC-HA protected almost all mice from disease development. Histological examination of the pancreata revealed significant reduction of peri-islet infiltrations in DEC-HA–treated mice, and the islet structure remained intact. Moreover, HA-specific CD4⁺ T-cells from anti–DEC-HA–treated INS-HA/TCR-HA mice exhibited increased expression of Foxp3, cytotoxic T-lymphocyte–associated antigen-4, and the immunosuppressive cytokines interleukin-10 and transforming growth factor-ß. The findings indicate that targeting of the HA antigen to immature dendritic cells in vivo leads to a relative increase of antigen-specific Foxp3⁺ regulatory T-cells that suppress the development of type 1 diabetes. Our results provide a basis for the development of novel strategies focusing on prevention rather than treatment of autoimmune diseases.

Abbreviations: CTLA, cytotoxic T-lymphocyte–associated antigen; DEC-HA, DEC-205 conjugated to the hemagglutinin antigen; HA, hemagglutinin; IL, interleukin; TCR, T-cell receptor; TGF, transforming growth factor; TRP2, tyrosinase-related protein-2

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. B. Stober, S. Brode, J. K. White, J.-F. Popoff, and J. M. Blackwell Slc11a1, Formerly Nramp1, Is Expressed in Dendritic Cells and Influences Major Histocompatibility Complex Class II Expression and Antigen-Presenting Cell Function Infect. Immun., October 1, 2007; 75(10): 5059 - 5067. [Abstract] [Full Text] [PDF]

				T. Enzler, S. Gillessen, M. Dougan, J. P. Allison, D. Neuberg, D. A. Oble, M. Mihm, and G. Dranoff Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of {beta} cells Blood, August 1, 2007; 110(3): 954 - 961. [Abstract] [Full Text] [PDF]

				W. Hansen, K. Loser, A. M. Westendorf, D. Bruder, S. Pfoertner, C. Siewert, J. Huehn, S. Beissert, and J. Buer G Protein-Coupled Receptor 83 Overexpression in Naive CD4+CD25- T Cells Leads to the Induction of Foxp3+ Regulatory T Cells In Vivo J. Immunol., July 1, 2006; 177(1): 209 - 215. [Abstract] [Full Text] [PDF]