title: Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs.
abstract: 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. However, 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 boosting 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.
authors.affiliation: 1Université Pierre et Marie Curie -- Univ Paris 06, France.
authors.forename: Yenkel
authors.initials: Y
authors.lastname: Grinberg-Bleyer
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Audrey
authors.initials: A
authors.lastname: Baeyens
authors.forename: Fabienne
authors.initials: F
authors.lastname: Billiard
authors.forename: Jérémie D
authors.initials: JD
authors.lastname: Goldstein
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grégoire
authors.forename: Gaëlle H
authors.initials: GH
authors.lastname: Martin
authors.forename: Rima
authors.initials: R
authors.lastname: Elhage
authors.forename: Nicolas
authors.initials: N
authors.lastname: Derian
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.forename: Gilles
authors.initials: G
authors.lastname: Marodon
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Eliane
authors.initials: E
authors.lastname: Piaggio
authors.forename: Benoît L
authors.initials: BL
authors.lastname: Salomon
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D025461:Feedback, Physiological; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell