Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus.
Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus.
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DOI：
10.1016/j.celrep.2016.10.013
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发表时间：
2016-11-01
期刊：
影响因子：
8.8
通讯作者：
Kassiotis G
中科院分区：
文献类型：
--
作者：
Donnarumma T;Young GR;Merkenschlager J;Eksmond U;Bongard N;Nutt SL;Boyer C;Dittmer U;Le-Trilling VT;Trilling M;Bayer W;Kassiotis G
CD4+ T 细胞会产生独特且通常相反的辅助、调节或细胞毒性活性。作为 CD8+ T 细胞的典型特性，颗粒酶介导的细胞毒性 T 细胞 (CTL) 潜力也由 CD4+ T 细胞发挥。然而，诱导 CD4+ CTL 的条件尚不完全清楚。使用单细胞转录分析，我们发现了颗粒酶 B (GzmB)+ CD4+ CTL 的独特特征，这将它们与其他 CD4+ T 辅助 (Th) 细胞（包括 Th1 细胞）区分开来，并与滤泡辅助 T (Tfh) 细胞特征形成强烈对比。 CD4+ CTL 和 Tfh 分化之间的平衡在很大程度上取决于感染病毒的类别，并受到 Tfh 相关转录因子 Bcl6 和 Tcf7（编码 TCF-1）以及抑制性受体 PD-1 和 LAG3 表达的共同调节。 CD4+ CTL 的这种独特特征为他们的研究提供了靶标，Tfh 程序对其的拮抗作用将 CD4+ T 细胞与辅助功能或杀伤功能分开。腺病毒启动具有 CTL 潜力的 CD4 T 细胞，但逆转录病毒则不然 CD4 CTL 在转录上与其他 Th 细胞不同 CD4 CTL 程序与 Tfh 程序直接相反 CD4 CTL 受到 TCF-1-Bcl6 连接以及 PD-1 和 LAG3“辅助”CD4 T 细胞的抑制 CD4 T 细胞也可以表现出颗粒酶介导的细胞毒性。唐纳鲁马等人。研究诱导 CD4 CTL 的条件并描述感染病毒类别的主导效应。他们发现了 CD4 CTL 的独特转录特征及其多层控制。
CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4+ CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4+ T cells with either helper or killer functions. Adenoviruses prime CD4 T cells with CTL potential, but retroviruses do not CD4 CTLs are transcriptionally distinguishable from other Th cells The CD4 CTL program is the direct opposite of the Tfh program CD4 CTLs are restrained by the TCF-1-Bcl6 nexus and by PD-1 and LAG3 “Helper” CD4 T cells can also exhibit granzyme-mediated cytotoxicity. Donnarumma et al. investigate the conditions that induce CD4 CTLs and describe the dominant effect of the class of infecting virus. They uncover a unique transcriptional signature of CD4 CTLs and its multi-layered control.
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DOI：
10.1084/jem.169.2.457
发表时间：
1989-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Klarnet JP;Kern DE;Okuno K;Holt C;Lilly F;Greenberg PD
通讯作者：
Greenberg PD
影响因子：
5.4
作者：
Bayer, Wibke;Tenbusch, Matthias;Wildner, Oliver
通讯作者：
Wildner, Oliver
影响因子：
16.6
作者：
Merkenschlager J;Ploquin MJ;Eksmond U;Andargachew R;Thorborn G;Filby A;Pepper M;Evavold B;Kassiotis G
通讯作者：
Kassiotis G
影响因子：
5.4
作者：
Hua, Laiqing;Yao, Shuyu;Sun, Jie
通讯作者：
Sun, Jie
影响因子：
5.8
作者：
Akhmetzyanova, Ilseyar;Zelinskyy, Gennadiy;Schimmer, Simone;Brandau, Sven;Altenhoff, Petra;Sparwasser, Tim;Dittmer, Ulf
通讯作者：
Dittmer, Ulf