KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.,Immunity

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KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.
Immunity ( IF 25.5 ) Pub Date : 2018-04-03 , DOI: 10.1016/j.immuni.2018.03.015
Dietmar Herndler-Brandstetter ₁ , Harumichi Ishigame ₂ , Ryo Shinnakasu ₃ , Valerie Plajer ₁ , Carmen Stecher ₁ , Jun Zhao ₄ , Melanie Lietzenmayer ₁ , Lina Kroehling ₁ , Akiko Takumi ₅ , Kohei Kometani ₆ , Takeshi Inoue ₇ , Yuval Kluger ₈ , Susan M Kaech ₁ , Tomohiro Kurosaki ₃ , Takaharu Okada ₉ , Richard A Flavell ₁₀

Affiliation

Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06511, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06511, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA; Applied Mathematics Program, Yale University, New Haven, CT 06511, USA.
Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.

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.

中文翻译：

KLRG1 +效应CD8 + T细胞失去KLRG1，分化为所有记忆T细胞谱系，并传递增强的保护性免疫力。

针对病原体的保护性免疫取决于功能多样的效应子和记忆T淋巴细胞的有效产生。但是，尚不清楚在效应子至记忆CD8 + T细胞分化过程中的可塑性是否会影响记忆谱系规范和功能多样性。使用对高度细胞毒性的KLRG1 +效应CD8 + T细胞的遗传命运定位分析，我们证明了在收缩期以Bach2依赖性方式，接受中等量的激活信号和炎症信号的KLRG1 +细胞下调了KLRG1的表达，并分化为所有记忆T细胞损伤，包括CX3CR1int外围存储单元和组织驻留存储单元。“ ExKLRG1”记忆细胞保留了不同于其他人群的高细胞毒性和增殖能力，有助于有效的抗流感和抗肿瘤免疫力。我们的工作表明，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方面很重要。

更新日期：2018-04-03

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