Exhausted CD8+ T cells face a developmental fork in the road

Ryan Zander*, Weiguo Cui

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


Reinvigorating the function of exhausted CD8+ T cells during chronic viral infection and cancer is a major goal of current immunotherapy regimens. Here, we discuss recent advances in our understanding of exhausted CD8+ T cell heterogeneity as well as the potential differentiation trajectories that exhausted T cells follow during chronic infection and/or cancer. We highlight surmounting evidence suggesting that some T cell clones are divergent in nature and can develop into either terminally differentiated effector or exhausted CD8+ T cells. Lastly, we consider the potential therapeutic implications of such a bifurcation model of CD8+ T cell differentiation, including the intriguing hypothesis that redirecting progenitor CD8+ T cell differentiation along an effector pathway may serve as a novel approach to mitigate T cell exhaustion.

Original languageEnglish (US)
Pages (from-to)276-286
Number of pages11
JournalTrends in Immunology
Issue number4
StatePublished - Apr 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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