@article {Xia2021.08.06.455141, author = {Yu Xia and Katalin Sandor and Joy A. Pai and Bence Daniel and Saravanan Raju and Renee Wu and Sunnie Hsiung and Yanyan Qi and Tenzin Yangdon and Mariko Okamoto and Robert D. Schreiber and Kenneth M. Murphy and Ansuman T. Satpathy and Takeshi Egawa}, title = {BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4 T cell responses to persistent antigen}, elocation-id = {2021.08.06.455141}, year = {2021}, doi = {10.1101/2021.08.06.455141}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Shortly after priming, the fate of activated CD4 T cells is segregated into BCL6+ follicular helper T (Tfh) and BCL6- effector (Teff) cells. However, it remains unknown how these subsets are sustained in the presence of chronic antigen stimulation. Using a combination of single cell- and population-based approaches, we show that in chronic viral infection, activated CD4 T cells differentiate into BCL6-dependent TCF-1+ progenitor cells with superior capacity to expand and give rise to both Teff and Tfh. They share properties with progenitor-exhausted CD8 T cells and are required for the continued generation of Teff cells as antigen persists. In response to tumors, an analogous CD4 T cell population develops in draining lymph nodes. Our study reveals the heterogeneity and plasticity of CD4 T cells upon encountering persistent antigen and highlights their population dynamics through a stable bipotent intermediate state.Competing Interest StatementA.T.S. is a scientific co-founder of Immunai and founder of Cartography Biosciences and receives research funding from Arsenal Biosciences and Allogene Therapeutics.}, URL = {https://www.biorxiv.org/content/early/2021/08/07/2021.08.06.455141}, eprint = {https://www.biorxiv.org/content/early/2021/08/07/2021.08.06.455141.full.pdf}, journal = {bioRxiv} }