Publikationsdatenbank

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

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bruder, Dunja

Westendorf, Astrid M

Hansen, Wiebke

Prettin, Silvia

Gruber, Achim D

Qian, Yingjie

von Boehmer, Harald

Mahnke, Karsten

Buer, Jan

Quelle

Diabetes

Bandzählung: 54

Heftzählung: 12

Seiten: 3395 – 3401

ISSN: 0012-1797

Sprache

Englisch

Verweise

Pubmed: 16306354

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

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.