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Human Peripheral Blood T Regulatory Cells (Tregs) Functionally Primed CCR4+ Tregs and Unprimed CCR4− Tregs Regulate Effector T Cells Using FasL

机译:人外周血T调节细胞(Treg)功能性引发的CCR4 + Treg和未引发的CCR4-Tregs使用FasL调节效应T细胞

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摘要

Regulatory CD25+ CD4+ T cells (Tregs) play an important role in the control of peripheral tolerance. In this study we demonstrate that human peripheral blood Tregs can be divided into two distinct populations based on the expression of CCR4. The majority (~75%) of freshly isolated Tregs express CCR4 and presumably represent memory-type Tregs. Interestingly, CCR4 Tregs require anti-CD3 Ab-mediated activation to acquire a regulatory activity, while CCR4+ Tregs appear to be already primed to suppress the proliferation of CD8+ T cells. CCR4 is also expressed on CD25lowCD4+ T cells (CCR4+ non-Tregs) that mostly suppress Th1-type polarization without affecting T cell proliferation, presumably via the production of immunomodulatory cytokines like IL-10. In contrast, CCR4+ Tregs express FasL to primarily regulate T cell proliferation via a contact-mediated process involving FasL/Fas signaling, a major regulatory pathway of T cell homeostasis. Finally, we also demonstrate that the depletion of CCR4+ T cells leads to Th1-type polarization of CD4+ T cells and augmentation of CD8+ T cell responses to tumor Ags.
机译:调节性CD25 + CD4 + T细胞(Tregs)在控制外周耐受中起重要作用。在这项研究中,我们证明了人类外周血Tregs可以基于CCR4的表达分为两个不同的群体。新鲜分离的Treg的大部分(〜75%)表达CCR4,大概代表记忆型Treg。有趣的是,CCR4 - Treg需要抗CD3 Ab介导的激活才能获得调节活性,而CCR4 + Tregs似乎已经被启动以抑制CD8 + T细胞。 CCR4也表达在CD25 low CD4 + T细胞(CCR4 + 非Treg)上,这些细胞主要抑制Th1型极化而不影响T细胞。可能是通过产生免疫调节细胞因子(如IL-10)来增殖。相反,CCR4 + Tregs通过FasL / Fas信号传导(T细胞稳态的主要调节途径)的接触介导过程表达FasL来主要调节T细胞增殖。最后,我们还证明了CCR4 + T细胞的耗竭导致CD4 + T细胞的Th1型极化和CD8 + 的增强T细胞对肿瘤Ags的反应。

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