PDF(Pubmed)
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.
摘要：
免疫反应的加剧和自身耐受性的丧失导致自身免疫和免疫病理学的发展。仍然需要靶向自身反应性T细胞的新疗法。这里,我们报道缺乏转录因子T-bet的Th2极化T细胞具有很强的免疫调节潜能,并通过IL-10抑制抗原特异性CD8+T细胞.Tbx21-/-Th2细胞保护小鼠免受病毒诱导的1型糖尿病的发展，不仅抑制幼稚，而且抑制记忆性CD8+T细胞反应。产生IL-10，但IL-10缺陷的Tbx21-/-Th2细胞在淋巴细胞脉络膜脑膜炎病毒感染后下调树突状细胞的共刺激分子并减少其IL-12的产生。受损的树突状细胞活化阻碍了感染后的效应子和细胞毒性CD8+T细胞发育。这些发现表明Tbx21-/-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。
