%0 Journal Article
%T Th2 cells lacking T-bet suppress naive and memory T cell responses via IL-10.
%A Muñoz M
%A Hegazy AN
%A Brunner TM
%A Holecska V
%A Marek RM
%A Fröhlich A
%A Löhning M
%J Proc Natl Acad Sci U S A
%V 118
%N 6
%D 02 2021 9
%M 33526653
%F 12.779
%R 10.1073/pnas.2002787118
%X Exacerbated immune responses and loss of self-tolerance lead to the development of autoimmunity and immunopathology. Novel therapies to target autoreactive T cells are still needed. Here, we report that Th2-polarized T cells lacking the transcription factor T-bet harbor strong immunomodulatory potential and suppress antigen-specific CD8+ T cells via IL-10. Tbx21-/- Th2 cells protected mice against virus-induced type 1 diabetes development and suppressed not only naive but also memory CD8+ T cell responses. IL-10-producing, but not IL-10-deficient Tbx21-/- Th2 cells down-regulated costimulatory molecules on dendritic cells and reduced their IL-12 production after lymphocytic choriomeningitis virus infection. Impaired dendritic cell activation hindered effector and cytotoxic CD8+ T cell development after infection. These findings indicate that Tbx21-/- Th2 cells strongly suppress proinflammatory responses of naive and memory T cells via IL-10. Thus, in vivo IL-10-secreting Th2 cells could harbor a therapeutic potential for the treatment of T cell-mediated inflammatory disorders.