Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center, Leibniz Institutes, 10117 Berlin, Germany.
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6). doi: 10.1073/pnas.2002787118.
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. 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 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 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.
免疫应答增强和自身耐受丧失导致自身免疫和免疫病理学的发展。仍然需要针对自身反应性 T 细胞的新型治疗方法。在这里，我们报告缺乏转录因子 T-bet 的 Th2 极化 T 细胞具有很强的免疫调节潜力，并通过 IL-10 抑制抗原特异性 CD8 T 细胞。Th2 细胞可保护小鼠免受病毒诱导的 1 型糖尿病的发展，并不仅抑制幼稚 CD8 T 细胞反应，而且抑制记忆 CD8 T 细胞反应。产生 IL-10 的 Th2 细胞，而不是缺乏 IL-10 的 Th2 细胞，在淋巴细胞性脉络丛脑膜炎病毒感染后下调树突状细胞上的共刺激分子，并减少其 IL-12 产生。树突状细胞激活受损阻碍了感染后效应和细胞毒性 CD8 T 细胞的发育。这些发现表明，Th2 细胞通过 IL-10 强烈抑制幼稚和记忆 T 细胞的促炎反应。因此，体内分泌 IL-10 的 Th2 细胞可能具有治疗 T 细胞介导的炎症性疾病的治疗潜力。
