Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs

Abstract

Research article 4558 The Journal of Clinical Investigation http://www.jci.org Volume 120 Number 12 December 2010 Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs Yenkel Grinberg-Bleyer,1,2,3 David Saadoun,1,2,3 Audrey Baeyens,1,2,3 Fabienne Billiard,1,2,3 Jérémie D. Goldstein,1,2,3 Sylvie Grégoire,1,2,3 Gaëlle H. Martin,1,2,3 Rima Elhage,1,2,3 Nicolas Derian,1,2,3 Wassila Carpentier,1,4 Gilles Marodon,1,2,3 David Klatzmann,1,2,3 Eliane Piaggio,1,2,3 and Benoît L. Salomon1,2,3 1Université Pierre et Marie Curie — Univ Paris 06, 2CNRS UMR 7211, 3INSERM U959, Paris, France. 4Plate-forme Post-Génomique P3S, Hôpital Pitié-Salpêtrière, Paris, France. CD4+CD25+Foxp3+ Tregs play a major role in prevention of autoimmune diseases. The suppressive effect of Tregs on effector T cells (Teffs), the cells that can mediate autoimmunity, has been extensively studied. How- ever, the in vivo impact of Teff activation on Tregs during autoimmunity has not been explored. In this study, we have shown that CD4+ Teff activation strongly boosts the expansion and suppressive activity of Tregs. This helper function of CD4+ T cells, which we believe to be novel, was observed in the pancreas and draining lymph nodes in mouse recipients of islet-specific Teffs and Tregs. Its physiological impact was assessed in autoimmune diabetes. When islet-specific Teffs were transferred alone, they induced diabetes. Paradoxically, when the same Teffs were cotransferred with islet-specific Tregs, they induced disease protection by boost- ing Treg expansion and suppressive function. RNA microarray analyses suggested that TNF family members were involved in the Teff-mediated Treg boost. In vivo experiments showed that this Treg boost was partially dependent on TNF but not on IL-2. This feedback regulatory loop between Teffs and Tregs may be critical to preventing or limiting the development of autoimmune diseases. Introduction The peripheral T cell repertoir

Key Biomarkers

Symptom Clusters