Human Peripheral Blood T Regulatory Cells (Tregs), Functionally Primed CCR4+ Tregs and Unprimed CCR4− Tregs, Regulate Effector T Cells Using FasL1
Human Peripheral Blood T Regulatory Cells (Tregs), Functionally Primed CCR4+ Tregs and Unprimed CCR4− Tregs, Regulate Effector T Cells Using FasL1
复制标题
人外周血 T 调节细胞 (Treg)、功能性引发的 CCR4+ Tregs 和未引发的 CCR4− Tregs，使用 FasL1 调节效应 T 细胞
作者：
D. Baatar;P. Olkhanud;K. Sumitomo;D. Taub;R. Gress;A. Biragyn
调节性CD25+CD4+T细胞(Tregs)在控制外周免疫耐受中起着重要作用。在这项研究中，我们证明了基于CCR4的表达，人类外周血树突状细胞可以分为两个不同的群体。大多数新鲜分离的树突状细胞(∼75%)表达CCR4CCR4，推测为记忆型树突状细胞。有趣的是，CCR4CD8+Tregs需要抗−抗体介导的激活才能获得调节活性，而CCR4+Tregs似乎已经准备好抑制CD8+T细胞的增殖。CCR4也表达在CD25lowCD4+T细胞(CCR4+非Tregs)上，这些细胞主要抑制Th1型极化，而不影响T细胞的增殖，推测是通过产生IL-10等免疫调节细胞因子来实现的。相反，CCR4+Tregs表达FasL主要是通过接触介导的过程来调节T细胞的增殖，该过程涉及到FasL/Fas信号，这是T细胞稳态的主要调节途径。最后，我们还证明了CCR4+T细胞的耗尽导致了CD4+T细胞的Th1型极化和CD8+T细胞对肿瘤AGS的反应增强。
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.
影响因子：
32.4
作者：
Grossman, WJ;Verbsky, JW;Ley, TJ
通讯作者：
Ley, TJ
用于测量 IGF-I、β-肌动蛋白和甘油醛 3-磷酸脱氢酶转录物的核糖探针表达盒。
影响因子：
2.2
作者：
Biragyn,A;Arkins,S;Kelley,KW
通讯作者：
Kelley,KW