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

ABSTRACT: 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.

SUBMITTER: Munoz M

PROVIDER: S-EPMC8017670 | biostudies-literature |

REPOSITORIES: biostudies-literature

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