Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2002787118
Keywords
autoimmunity T-bet; IL-10; CD8(+) T cells; memory responses
Categories
Funding
- German Research Foundation [SFB650, TP28, LO 1542/3-1, LO 1542/4-1, CRC-TRR241]
- European Union
- Volkswagen Foundation
- Willy Robert Pitzer Foundation (Osteoarthritis Research Program)
- Charite-Universitatsmedizin Berlin
- BIH
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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.
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.
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