TGF-β regulates the stem-like state of PD-1+ TCF-1+ virus-specific CD8 T cells during chronic infection

Yinghong Hu, William H. Hudson, Haydn T. Kissick, Christopher B. Medina, Antonio P. Baptista, Chaoyu Ma, Wei Liao, Ronald N. Germain, Shannon J. Turley, Nu Zhang, Rafi Ahmed

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Recent studies have defined a novel population of PD-1+ TCF-1+ stem-like CD8 T cells in chronic infections and cancer. These quiescent cells reside in lymphoid tissues, are critical for maintaining the CD8 T cell response under conditions of persistent antigen, and provide the proliferative burst after PD-1 blockade. Here we examined the role of TGF-β in regulating the differentiation of virus-specific CD8 T cells during chronic LCMV infection of mice. We found that TGF-β signaling was not essential for the generation of the stem-like CD8 T cells but was critical for maintaining the stem-like state and quiescence of these cells. TGF-β regulated the unique transcriptional program of the stem-like subset, including upregulation of inhibitory receptors specifically expressed on these cells. TGF-β also promoted the terminal differentiation of exhausted CD8 T cells by suppressing the effector-associated program. Together, the absence of TGF-β signaling resulted in significantly increased accumulation of effector-like CD8 T cells. These findings have implications for immunotherapies in general and especially for T cell therapy against chronic infections and cancer.

Original languageEnglish (US)
Article numbere20211574
JournalJournal of Experimental Medicine
Issue number10
StatePublished - Oct 3 2022

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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