1. Induction of antigen-specific Treg cells in treating autoimmune uveitis via bystander suppressive pathways without compromising anti-tumor immunity.
- Author
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Chen Z, Zhang T, Kam HT, Qiao D, Jin W, Zhong Y, Zhou M, Zhou H, Chong WP, Chen W, and Chen J
- Subjects
- Animals, Autoantigens immunology, Autoimmune Diseases immunology, Cell Line, Tumor, Cells, Cultured, Eye Proteins immunology, Interleukin-10 metabolism, Mice, Mice, Inbred C57BL, Retinol-Binding Proteins immunology, Transforming Growth Factor beta metabolism, Uveitis immunology, Autoimmune Diseases therapy, Bystander Effect, Immunosuppression Therapy methods, T-Lymphocytes, Regulatory immunology, Uveitis therapy
- Abstract
Background: Induction of autoantigen-specific Treg cells that suppress tissue-specific autoimmunity without compromising beneficial immune responses is the holy-grail for immunotherapy to autoimmune diseases., Methods: In a model of experimental autoimmune uveitis (EAU) that mimics human uveitis, ocular inflammation was induced by immunization with retinal antigen interphotoreceptor retinoid-binding protein (IRBP). Mice were given intraperitoneal injection of αCD4 antibody (Ab) after the onset of disease, followed by administration of IRBP. EAU was evaluated clinically and functionally. Splenocytes, CD4
+ CD25- and CD4+ CD25+ T cells were sorted and cultured with IRBP or αCD3 Ab. T cell proliferation and cytokine production were assessed., Findings: The experimental approach resulted in remission of ocular inflammation and rescue of visual function in mice with established EAU. Mechanistically, the therapeutic effect was mediated by induction of antigen-specific Treg cells that inhibited IRBP-driven Th17 response in TGF-β and IL-10 dependent fashion. Importantly, the Ab-mediated immune tolerance could be achieved in EAU mice by administration of retinal autoantigens, arrestin but not limited to IRBP only, in an antigen-nonspecific bystander manner. Further, these EAU-suppressed tolerized mice did not compromise their anti-tumor T immunity in melanoma model., Interpretation: We successfully addressed a specific immunotherapy of EAU by in vivo induction of autoantigen-specific Treg cells without compromising host overall T cell immunity, which should have potential implication for patients with autoimmune uveitis., Funding: This study was supported by the Natural Science Foundation of Guangdong Province and the Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center., Competing Interests: Declaration of Competing Interest Patents (ZL201711202986.0 and ZL201711202988.X) for the reported data are granted in China. The authors have declared that no conflict of interest exists., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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