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

被引：322

作者：

Herndler-Brandstetter, Dietmar ^{[1
,11
]}

Ishigame, Harumichi ^{[1
,2
]}

Shinnakasu, Ryo ^{[3
,4
]}

Plajer, Valerie ^{[1
]}

Stecher, Carmen ^{[1
]}

Zhao, Jun ^{[1
,5
,6
]}

Lietzenmayer, Melanie ^{[1
]}

Kroehling, Lina ^{[1
]}

Takumi, Akiko ^{[2
]}

Kometani, Kohei ^{[3
,10
]}

Inoue, Takeshi ^{[4
]}

Kluger, Yuval ^{[5
,6
,7
]}

Kaech, Susan M. ^{[1
]}

Kurosaki, Tomohiro ^{[3
,4
]}

Okada, Takaharu ^{[2
,8
,9
]}

Flavell, Richard A. ^{[1
,10
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA

[2] RIKEN Ctr Integrat Med Sci, Lab Tissue Dynam, Yokohama, Kanagawa 2300045, Japan

[3] RIKEN Ctr Integrat Med Sci, Lab Lymphocyte Differentiat, Yokohama, Kanagawa 2300045, Japan

[4] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Lymphocyte Differentiat, Suita, Osaka 5650871, Japan

[5] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06511 USA

[6] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06511 USA

[7] Yale Univ, Appl Math Program, New Haven, CT 06511 USA

[8] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan

[9] Yokohama City Univ, Grad Sch Med Life Sci, Yokohama, Kanagawa 2300045, Japan

[10] Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06520 USA

[11] Med Univ Vienna, Inst Canc Res, A-1090 Vienna, Austria

来源：

IMMUNITY | 2018年 / 48卷 / 04期

基金：

日本科学技术振兴机构; 奥地利科学基金会;

关键词：

TRANSCRIPTION FACTORS; TERMINAL DIFFERENTIATION; LYMPHOID ORGANS; SUBSETS; EXPRESSION; CHROMATIN; ANTIGEN; REPRESSION; POPULATION; INDUCTION;

D O I：

10.1016/j.immuni.2018.03.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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 CX(3)CR1(int) 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.

引用

页码：716 / +

页数：22

共 62 条

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