Transcriptional Reprogramming of Mature CD4(+) T helper Cells generates distinct MHC class II-restricted Cytotoxic T Lymphocytes

TCRαβ thymocytes differentiate to either CD8αβ cytotoxic T lymphocytes or CD4(+) T helper cells. This functional dichotomy is controlled by key transcription factors, including the T helper master regulator, ThPOK, which suppresses the cytolytic program in MHC class II-restricted CD4(+) thymocytes....

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Detalles Bibliográficos
Autores principales: Mucida, Daniel, Husain, Mohammad Mushtaq, Muroi, Sawako, van Wijk, Femke, Shinnakasu, Ryo, Naoe, Yoshinori, Reis, Bernardo Sgarbi, Huang, Yujun, Lambolez, Florence, Docherty, Michael, Attinger, Antoine, Shui, Jr-Wen, Kim, Gisen, Lena, Christopher J., Sakaguchi, Shinya, Miyamoto, Chizuko, Wang, Peng, Atarashi, Koji, Park, Yunji, Nakayama, Toshinori, Honda, Kenya, Ellmeier, Wilfried, Kronenberg, Mitchell, Taniuchi, Ichiro, Cheroutre, Hilde
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581083/
https://www.ncbi.nlm.nih.gov/pubmed/23334788
http://dx.doi.org/10.1038/ni.2523
Descripción
Sumario:TCRαβ thymocytes differentiate to either CD8αβ cytotoxic T lymphocytes or CD4(+) T helper cells. This functional dichotomy is controlled by key transcription factors, including the T helper master regulator, ThPOK, which suppresses the cytolytic program in MHC class II-restricted CD4(+) thymocytes. ThPOK continues to repress CD8-lineage genes in mature CD4(+) T cells, even as they differentiate to T helper effector subsets. Here we show that the T helper-fate was not fixed and that mature antigen-stimulated CD4(+) T cells could terminate Thpok expression and reactivate CD8-lineage genes. This unexpected plasticity resulted in the post-thymic termination of the T helper-program and the functional differentiation of distinct MHC class II-restricted CD4(+) cytotoxic T lymphocytes.

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