학술논문
The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes
Document Type
article
Author
Yasmina Serroukh; Chunyan Gu-Trantien; Baharak Hooshiar Kashani; Matthieu Defrance; Thien-Phong Vu Manh; Abdulkader Azouz; Aurélie Detavernier; Alice Hoyois; Jishnu Das; Martin Bizet; Emeline Pollet; Tressy Tabbuso; Emilie Calonne; Klaas van Gisbergen; Marc Dalod; François Fuks; Stanislas Goriely; Arnaud Marchant
Source
eLife, Vol 7 (2018)
Subject
Language
English
ISSN
2050-084X
Abstract
Cytotoxic CD4 (CD4CTX) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant proportion of CD4 T cells displays cytotoxic functions. We observed that the transcriptional program of these cells was enriched in CD8 T cell lineage genes despite the absence of ThPOK downregulation. We further show that establishment of CD4CTX-specific transcriptional and epigenetic programs occurred in a stepwise fashion along the Th1-differentiation pathway. In vitro, prolonged activation of naive CD4 T cells in presence of Th1 polarizing cytokines led to the acquisition of perforin-dependent cytotoxic activity. This process was dependent on the Th1 transcription factor Runx3 and was limited by the sustained expression of ThPOK. This work elucidates the molecular program of human CD4CTX T cells and identifies potential targets for immunotherapy against viral infections and cancer.