Transcriptional Reprogramming of Mature CD4⁺ Helper T Cells Generates Distinct MHC Class II-restricted Cytotoxic T Lymphocytes

Overview

Journal Nat Immunol

Date 2013 Jan 22

PMID 23334788

Citations 200

Authors

Daniel Mucida

Mohammad Mushtaq Husain

Sawako Muroi

Femke van Wijk

Ryo Shinnakasu

Yoshinori Naoe

Bernardo Sgarbi Reis

Yujun Huang

Florence Lambolez

Michael Docherty

Antoine Attinger

Jr-Wen Shui

Gisen Kim

Christopher J Lena

Shinya Sakaguchi

Chizuko Miyamoto

Peng Wang

Koji Atarashi

Yunji Park

Toshinori Nakayama

Kenya Honda

Wilfried Ellmeier

Mitchell Kronenberg

Ichiro Taniuchi

Hilde Cheroutre

Affiliations

Soon will be listed here.

Abstract

TCRαβ thymocytes differentiate into either CD8αβ(+) 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.

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