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
Summary:
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.
Source:
Nature Immunology; 14, 281-289 (01/20/13)