Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection

Michael A. Paley, Daniela C. Kroy, Pamela M. Odorizzi, Jonathan B. Johnnidis, Douglas V. Dolfi, Burton E. Barnett, Elizabeth K. Bikoff, Elizabeth J. Robertson, Georg M. Lauer, Steven L. Reiner, E. John Wherry

Research output: Contribution to journalArticlepeer-review

633 Scopus citations


Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and molecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific CD8+ T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD8+ T cells during chronic viral infection. T-bethi cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to Eomeshi terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections.

Original languageEnglish
Pages (from-to)1220-1225
Number of pages6
Issue number6111
StatePublished - Nov 30 2012


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