Fachbereich Veterinärmedizin



    On the Edge of Autoimmunity:
    T-Cell Stimulation by Steady-state Dendritic Cells Prevents Autoimmune Diabetes (2005)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Bruder, Dunja
    Westendorf, Astrid M
    Hansen, Wiebke
    Prettin, Silvia
    Gruber, Achim D
    Qian, Yingjie
    von Boehmer, Harald
    Mahnke, Karsten
    Buer, Jan
    Diabetes; 54(12) — S. 3395–3401
    ISSN: 0012-1797
    Pubmed: 16306354
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
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    Abstract / Zusammenfassung

    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 approximately 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-beta. 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.