Transcriptional reprogramming of mature CD4+ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes

被引：275

作者：

Mucida, Daniel ^{[1
]}

Husain, Mohammad Mushtaq ^{[1
]}

Muroi, Sawako ^{[2
]}

van Wijk, Femke ^{[1
]}

Shinnakasu, Ryo ^{[1
]}

Naoe, Yoshinori ^{[2
]}

Reis, Bernardo Sgarbi ^{[3
]}

Huang, Yujun ^{[1
]}

Lambolez, Florence ^{[1
]}

Docherty, Michael ^{[1
]}

Attinger, Antoine ^{[1
]}

Shui, Jr-Wen ^{[1
]}

Kim, Gisen ^{[1
]}

Lena, Christopher J. ^{[1
]}

Sakaguchi, Shinya ^{[4
]}

Miyamoto, Chizuko ^{[2
]}

Wang, Peng ^{[5
]}

Atarashi, Koji ^{[6
]}

Park, Yunji ^{[1
]}

Nakayama, Toshinori ^{[7
]}

Honda, Kenya ^{[6
]}

Ellmeier, Wilfried ^{[4
]}

Kronenberg, Mitchell ^{[1
]}

Taniuchi, Ichiro ^{[2
]}

Cheroutre, Hilde ^{[1
]}

机构：

[1] La Jolla Inst Allergy Immunol, Div Dev Immunol, La Jolla, CA 92037 USA

[2] RIKEN Res Ctr Allergy & Immunol, Lab Transcript Regulat, Yokohama, Kanagawa, Japan

[3] Rockefeller Univ, Lab Mucosal Immunol, New York, NY 10021 USA

[4] Med Univ Vienna, Ctr Physiol Pathophysiol & Immunol, Inst Immunol, Vienna, Austria

[5] La Jolla Inst Allergy Immunol, Div Vaccine Discovery, La Jolla, CA USA

[6] Univ Tokyo, Grad Sch Med, Dept Immunol, Tokyo, Japan

[7] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba, Japan

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 03期

基金：

奥地利科学基金会; 美国国家卫生研究院; 日本学术振兴会;

关键词：

INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; CD8; INTERLEUKIN-15; EXPRESSION; DIFFERENTIATION; IDENTIFICATION; REPRESSION; RESPONSES; GATA-3; THPOK;

D O I：

10.1038/ni.2523

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

TCR alpha beta thymocytes differentiate into either CD8 alpha beta(+) cytotoxic T lymphocytes or CD4(+) helper T cells. This functional dichotomy is controlled by key transcription factors, including the helper T cell master regulator ThPOK, which suppresses the cytolytic program in major histocompatibility complex (MHC) class II-restricted CD4(+) thymocytes. ThPOK continues to repress genes of the CD8 lineage in mature CD4(+) T cells, even as they differentiate into effector helper T cell subsets. Here we found that the helper T cell fate was not fixed and that mature, antigen-stimulated CD4(+) T cells terminated expression of the gene encoding ThPOK and reactivated genes of the CD8 lineage. This unexpected plasticity resulted in the post-thymic termination of the helper T cell program and the functional differentiation of distinct MHC class II-restricted CD4(+) cytotoxic T lymphocytes.

引用

页码：281 / 289

页数：9

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