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

Yu Xia, Katalin Sandor, Joy A. Pai, Bence Daniel, Saravanan Raju, Renee Wu, Sunnie Hsiung, Yanyan Qi, Tenzin Yangdon, Mariko Okamoto, Chun Chou, Kamir J. Hiam-Galvez, Robert D. Schreiber, Kenneth M. Murphy, Ansuman T. Satpathy, Takeshi Egawa

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Soon after activation, CD4+ T cells are segregated into BCL6+ follicular helper (Tfh) and BCL6 effector (Teff) T cells. Here, we explored how these subsets are maintained during chronic antigen stimulation using the mouse chronic LCMV infection model. Using single cell-transcriptomic and epigenomic analyses, we identified a population of PD-1+ TCF-1+ CD4+ T cells with memory-like features. TCR clonal tracing and adoptive transfer experiments demonstrated that these cells have self-renewal capacity and continue to give rise to both Teff and Tfh cells, thus functioning as progenitor cells. Conditional deletion experiments showed Bcl6-dependent development of these progenitors, which were essential for sustaining antigen-specific CD4+ T cell responses to chronic infection. An analogous CD4+ T cell population developed in draining lymph nodes in response to tumors. Our study reveals the heterogeneity and plasticity of CD4+ T cells during persistent antigen exposure and highlights their population dynamics through a stable, bipotent intermediate state.

Original languageEnglish
Pages (from-to)1200-1215.e6
JournalImmunity
Volume55
Issue number7
DOIs
StatePublished - Jul 12 2022

Keywords

  • anti-tumor immunity
  • CD4 T cells
  • chronic viral infection
  • effector T cells
  • follicular helper T cells
  • progenitor cells
  • single-cell genomics

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