title: Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes.
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.
authors: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California, USA.
authors: Daniel
authors: D
authors: Mucida
authors: Mohammad Mushtaq
authors: MM
authors: Husain
authors: Sawako
authors: S
authors: Muroi
authors: Femke
authors: F
authors: van Wijk
authors: Ryo
authors: R
authors: Shinnakasu
authors: Yoshinori
authors: Y
authors: Naoe
authors: Bernardo Sgarbi
authors: BS
authors: Reis
authors: Yujun
authors: Y
authors: Huang
authors: Florence
authors: F
authors: Lambolez
authors: Michael
authors: M
authors: Docherty
authors: Antoine
authors: A
authors: Attinger
authors: Jr-Wen
authors: JW
authors: Shui
authors: Gisen
authors: G
authors: Kim
authors: Christopher J
authors: CJ
authors: Lena
authors: Shinya
authors: S
authors: Sakaguchi
authors: Chizuko
authors: C
authors: Miyamoto
authors: Peng
authors: P
authors: Wang
authors: Koji
authors: K
authors: Atarashi
authors: Yunji
authors: Y
authors: Park
authors: Toshinori
authors: T
authors: Nakayama
authors: Kenya
authors: K
authors: Honda
authors: Wilfried
authors: W
authors: Ellmeier
authors: Mitchell
authors: M
authors: Kronenberg
authors: Ichiro
authors: I
authors: Taniuchi
authors: Hilde
authors: H
authors: Cheroutre
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D044082:Citrobacter rodentium / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D015851:Interleukin-7 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D015851:Interleukin-7; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse; C064658:RAG-1 protein