Th2 cells lacking T-bet suppress naive and memory T cell responses via IL-10

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 downregulated 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.

Automated summary

Th2 cells lacking T-bet exhibit strong immunomodulatory potential by suppressing antigen-specific CD8(+) T cell responses via IL-10. These cells protect mice against virus-induced type 1 diabetes and hinder effector and cytotoxic CD8(+) T cell development by downregulating dendritic cell activation. IL-10-secreting Th2 cells could potentially be used as a therapeutic approach for T cell-mediated inflammatory disorders.