par Serroukh, Yasmina 
;Gu-Trantien, Chunyan ;Hooshiar Kashani, Baharak ;Defrance, Matthieu ;Vu Manh, Thien-Phong;Azouz, Abdulkader ;Detavernier, Aurélie ;Hoyois, Alice ;Das, Jishnu;Bizet, Martin ;Pollet, Emeline;Tabbuso, Tressy ;Calonne, Emilie ;van Gisbergen, Klaas;Dalod, Marc;Fuks, François ;Goriely, Stanislas ;Marchant, Arnaud
Référence eLife, 7
Publication Publié, 2018-02
;Gu-Trantien, Chunyan ;Hooshiar Kashani, Baharak ;Defrance, Matthieu ;Vu Manh, Thien-Phong;Azouz, Abdulkader ;Detavernier, Aurélie ;Hoyois, Alice ;Das, Jishnu;Bizet, Martin ;Pollet, Emeline;Tabbuso, Tressy ;Calonne, Emilie ;van Gisbergen, Klaas;Dalod, Marc;Fuks, François ;Goriely, Stanislas ;Marchant, Arnaud Référence eLife, 7
Publication Publié, 2018-02
Article révisé par les pairs
| Résumé : | Cytotoxic CD4 (CD4CTX) T cells are emerging as an important component of anti-viral and anti-tumor 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 CD4CTXT cells and identifies potential targets for immunotherapy against viral infections and cancer. |
