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The epigenetic landscape of T cell exhaustion

by Godec, Jernej , Chung, Raymond T. , Kaminski, James , Gerdemann, Ulrike , Wherry, E. John , Lauer, Georg M. , Tsao, Hsiao-Wei , Barnitz, R. Anthony , Yates, Kathleen B. , LaFleur, Martin W. , Frahm, Nicole , Allen, Todd M. , Tully, Damien C. , Haining, W. Nicholas , Tonnerre, Pierre , Brown, Flavian D. , Sen, Debattama R. , Kurachi, Makoto , Yosef, Nir

in Animals / B7-H1 Antigen - antagonists & inhibitors / B7-H1 Antigen - genetics / Cancer / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - transplantation / Cell Lineage - genetics / Chromatin - immunology / Chronic Disease / Disease Models, Animal / Editing / Enhancer Elements, Genetic / Epigenesis, Genetic / Epigenetics / Gene Editing / Gene expression / Genes / Genomes / Genotype & phenotype / Hepatitis C, Chronic - therapy / HIV Infections - therapy / Humans / Immunologic Memory - genetics / Immunotherapy / Infections / Landscapes / Lymphocytes / Lymphocytic Choriomeningitis - therapy / Mice / Mice, Inbred C57BL / Modules / SOXB1 Transcription Factors - metabolism / T-Box Domain Proteins - metabolism / Transcription, Genetic

2016

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The epigenetic landscape of T cell exhaustion

2016

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2016

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Journal Article

The epigenetic landscape of T cell exhaustion

Godec, Jernej,

Chung, Raymond T.,

Kaminski, James,

Gerdemann, Ulrike,

Wherry, E. John,

Lauer, Georg M.,

Tsao, Hsiao-Wei,

Barnitz, R. Anthony,

Yates, Kathleen B.,

LaFleur, Martin W.,

Frahm, Nicole,

Allen, Todd M.,

Tully, Damien C.,

Haining, W. Nicholas,

Tonnerre, Pierre,

Brown, Flavian D.,

Sen, Debattama R.,

Kurachi, Makoto,

Yosef, Nir

2016

Overview

Exhausted T cells in cancer and chronic viral infection express distinctive patterns of genes, including sustained expression of programmed cell death protein 1 (PD-1). However, the regulation of gene expression in exhausted T cells is poorly understood. Here, we define the accessible chromatin landscape in exhausted CD8⁺ T cells and show that it is distinct from functional memory CD8⁺ T cells. Exhausted CD8⁺ T cells in humans and a mouse model of chronic viral infection acquire a state-specific epigenetic landscape organized into functional modules of enhancers. Genome editing snows that PD-1 expression is regulated in part by an exhaustion-specific enhancer that contains essential RAR, T-bet, and Sox3 motifs. Functional enhancer maps may offer targets for genome editing that alter gene expression preferentially in exhausted CD8⁺ T cells.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

Animals

/ B7-H1 Antigen - antagonists & inhibitors

/ B7-H1 Antigen - genetics

/ Cancer

/ CD8-Positive T-Lymphocytes - immunology

/ CD8-Positive T-Lymphocytes - transplantation

/ Cell Lineage - genetics