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 Nakayama; Kenya Honda; Wilfried Ellmeier; Mitchell Kronenberg; Ichiro Taniuchi; Hilde Cheroutre

doi:10.1038/ni.2523

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

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

230 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 language	English
Pages (from-to)	281-289
Number of pages	9
Journal	Nature Immunology
Volume	14
Issue number	3
DOIs	https://doi.org/10.1038/ni.2523
Publication status	Published - 2013 Mar

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni.2523

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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/ni.2523

Mucida, D, Husain, MM, Muroi, S, Van Wijk, F, Shinnakasu, R, Naoe, Y, Reis, BS, Huang, Y, Lambolez, F, Docherty, M, Attinger, A, Shui, JW, Kim, G, Lena, CJ, Sakaguchi, S, Miyamoto, C, Wang, P, Atarashi, K, Park, Y, Nakayama, T, Honda, K, Ellmeier, W, Kronenberg, M, Taniuchi, I & Cheroutre, H 2013, 'Transcriptional reprogramming of mature CD4 + helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes', Nature Immunology, vol. 14, no. 3, pp. 281-289. https://doi.org/10.1038/ni.2523

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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.",

author = "Daniel Mucida and Husain, {Mohammad Mushtaq} and Sawako Muroi and {Van Wijk}, Femke and Ryo Shinnakasu and Yoshinori Naoe and Reis, {Bernardo Sgarbi} and Yujun Huang and Florence Lambolez and Michael Docherty and Antoine Attinger and Shui, {Jr Wen} and Gisen Kim and Lena, {Christopher J.} and Shinya Sakaguchi and Chizuko Miyamoto and Peng Wang and Koji Atarashi and Yunji Park and Toshinori Nakayama and Kenya Honda and Wilfried Ellmeier and Mitchell Kronenberg and Ichiro Taniuchi and Hilde Cheroutre",

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AU - Husain, Mohammad Mushtaq

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AU - Van Wijk, Femke

AU - Shinnakasu, Ryo

AU - Naoe, Yoshinori

AU - Reis, Bernardo Sgarbi

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AU - Docherty, Michael

AU - Attinger, Antoine

AU - Shui, Jr Wen

AU - Kim, Gisen

AU - Lena, Christopher J.

AU - Sakaguchi, Shinya

AU - Miyamoto, Chizuko

AU - Wang, Peng

AU - Atarashi, Koji

AU - Park, Yunji

AU - Nakayama, Toshinori

AU - Honda, Kenya

AU - Ellmeier, Wilfried

AU - Kronenberg, Mitchell

AU - Taniuchi, Ichiro

AU - Cheroutre, Hilde

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

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