Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory

• Published in: The Journal of immunology (1950) Vol. 198; no. 6; pp. 2238 - 2243
• Main Authors: Scharer, Christopher D, Bally, Alexander P R, Gandham, Bhanu, Boss, Jeremy M
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15.03.2017
• Subjects: Animals; Arenaviridae; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Proliferation; Cells, Cultured; Chromatin; Chromatin - immunology; Chromatin Assembly and Disassembly; Gene expression; Genes; Immunologic Memory - genetics; Immunological memory; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Lymphocytic Choriomeningitis - immunology; Lymphocytic choriomeningitis virus - immunology; Memory cells; Mice; Mice, Inbred C57BL; Molecular modelling; Regulatory sequences; Sequence Analysis, DNA; T cell receptors; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - virology; Transposase; Transposases - metabolism; Viruses
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1602086

CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the -regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor-binding motifs. Memory CD8 T cells displayed a chromatin accessibility structure that was absent from other acute and exhausted cells types and included key effector and proliferative genes. Stimulation of memory cells revealed enhanced transcription of "memory-primed" genes compared with naive cells. Thus, memory CD8 T cells display a preprogrammed chromatin accessibility profile and maintain a molecular history of -element usage, thereby reducing the steps necessary to revive effector functions.