Progenitor and Terminal Subsets of CD8 + T Cells Cooperate to Contain Chronic Viral Infection
Top Cited Papers
- 30 November 2012
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 338 (6111), 1220-1225
- https://doi.org/10.1126/science.1229620
Abstract
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.Keywords
This publication has 41 references indexed in Scilit:
- The Transcription Factors T-bet and Eomes Control Key Checkpoints of Natural Killer Cell MaturationImmunity, 2012
- Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infectionNature Immunology, 2011
- Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infectionProceedings of the National Academy of Sciences of the United States of America, 2010
- A Role for the Transcriptional Repressor Blimp-1 in CD8+ T Cell Exhaustion during Chronic Viral InfectionImmunity, 2009
- Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infectionNature Immunology, 2008
- Functional Restoration of HCV-Specific CD8 T Cells by PD-1 Blockade Is Defined by PD-1 Expression and CompartmentalizationGastroenterology, 2008
- Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cellsThe Journal of Experimental Medicine, 2007
- Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription FactorImmunity, 2007
- Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infectionThe Journal of Experimental Medicine, 2007
- Lineage relationship and protective immunity of memory CD8 T cell subsetsNature Immunology, 2003