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

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 NakayamaKenya Honda, Wilfried Ellmeier, Mitchell Kronenberg, Ichiro Taniuchi, Hilde Cheroutre

Research output: Contribution to journalArticle

151 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalNature Immunology
Volume14
Issue number3
DOIs
Publication statusPublished - 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Mucida, D., Husain, M. M., Muroi, S., Van Wijk, F., Shinnakasu, R., Naoe, Y., Reis, B. S., Huang, Y., Lambolez, F., Docherty, M., Attinger, A., Shui, J. W., Kim, G., Lena, C. J., Sakaguchi, S., Miyamoto, C., Wang, P., Atarashi, K., Park, Y., ... Cheroutre, H. (2013). Transcriptional reprogramming of mature CD4 + helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes. Nature Immunology, 14(3), 281-289. https://doi.org/10.1038/ni2523