BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4 T cell responses to persistent antigen

Xia, Y.; Sandor, K.; Pai, J. A.; Daniel, B.; Raju, S.; Wu, R.; Hsiung, S.; Qi, Y.; Yangdon, T.; Okamoto, M.; Schreiber, R. D.; Murphy, K. M.; Satpathy, A. T.; Egawa, T.

doi:10.1101/2021.08.06.455141

bioRxiv · 10.1101/2021.08.06.455141

BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4 T cell responses to persistent antigen

Xia, Y.·Sandor, K.·Pai, J. A.·Daniel, B.·Raju, S.·Wu, R.·Hsiung, S.·Qi, Y.·Yangdon, T.·Okamoto, M.·Schreiber, R. D.·Murphy, K. M.·Satpathy, A. T.·Egawa, T.

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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.

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Xia, Y., Sandor, K., Pai, J. A., Daniel, B., Raju, S., Wu, R., Hsiung, S., Qi, Y., Yangdon, T., Okamoto, M., Schreiber, R. D., Murphy, K. M., Satpathy, A. T., Egawa, T.. 2021-08-09. BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4 T cell responses to persistent antigen. https://doi.org/10.1101/2021.08.06.455141

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