KLRG1(+) Effector CD8(+) T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.
KLRG1(+) Effector CD8(+) T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.
复制标题
DOI：
10.1016/j.immuni.2018.03.015
复制
发表时间：
2018-04-17
期刊：
影响因子：
32.4
通讯作者：
Flavell RA
中科院分区：
文献类型：
--
作者：
Herndler-Brandstetter D;Ishigame H;Shinnakasu R;Plajer V;Stecher C;Zhao J;Lietzenmayer M;Kroehling L;Takumi A;Kometani K;Inoue T;Kluger Y;Kaech SM;Kurosaki T;Okada T;Flavell RA
对病原体的保护性免疫依赖于功能多样的效应T淋巴细胞和记忆T淋巴细胞的有效产生。然而，效应体-记忆CD8+ T细胞分化过程中的可塑性是否影响记忆谱系规格和功能多功能性尚不清楚。通过对高细胞毒性KLRG1+效应CD8+ T细胞的遗传命运定位分析，我们证明了KLRG1+细胞接受中等数量的激活和炎症信号，在收缩阶段以bach2依赖的方式下调KLRG1，并分化为所有记忆T细胞谱系，包括CX3CR1int外周记忆细胞和组织驻留记忆细胞。“ExKLRG1”记忆细胞保留了与其他细胞群不同的高细胞毒性和增殖能力，这有助于有效的抗流感和抗肿瘤免疫。我们的研究表明，KLRG1+效应CD8+ T细胞的发育可塑性在促进功能多样的记忆细胞和长期保护性免疫中是重要的。Herndler-Brandstetter等人证明，KLRG1+ IL-7Rα+效应CD8+ T细胞以bach2依赖性的方式下调KLRG1，并分化为长寿的循环和组织驻留的“exKLRG1”记忆细胞。因此，KLRG1+效应细胞的发育可塑性驱动记忆T细胞谱系内的功能多样性，并促进抗流感和抗肿瘤免疫的增强。
Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8+ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8+ T cells, we demonstrated that KLRG1+ cells receiving intermediate amounts of activating and inflammatory signals, downregulated KLRG1 during the contraction phase in a Bach2-dependent manner, and differentiated into all memory T cell linages, including CX3CR1int peripheral memory cells and tissue-resident memory cells. ‘ExKLRG1’ memory cells retained high cytotoxic and proliferative capacity distinct from other populations, which contributed to effective anti-influenza and anti-tumor immunity. Our work demonstrates that developmental plasticity of KLRG1+ effector CD8+ T cells is important in promoting functionally versatile memory cells and long-term protective immunity. Herndler-Brandstetter et al. demonstrate that KLRG1+ IL-7Rα+ effector CD8+ T cells downregulate KLRG1 in a Bach2-depenent manner and differentiate into long-lived circulating and tissue-resident ‘exKLRG1’ memory cells. Developmental plasticity of KLRG1+ effector cells therefore drives functional diversity within memory T cell lineages and promotes enhanced anti-influenza and anti-tumor immunity.
登录
查看更多内容
影响因子：
8.8
作者：
Chu T;Tyznik AJ;Roepke S;Berkley AM;Woodward-Davis A;Pattacini L;Bevan MJ;Zehn D;Prlic M
通讯作者：
Prlic M
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.4
作者：
Endrizzi, BT;Jameson, SC
通讯作者：
Jameson, SC
影响因子：
4.4
作者：
Hara, Takahiro;Shitara, Soichiro;Ikuta, Koichi
通讯作者：
Ikuta, Koichi
影响因子：
64.8
作者：
Araki, Koichi;Turner, Alexandra P.;Shaffer, Virginia Oliva;Gangappa, Shivaprakash;Keller, Susanne A.;Bachmann, Martin F.;Larsen, Christian P.;Ahmed, Rafi
通讯作者：
Ahmed, Rafi