Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory.
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 thecis-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 ofcis-element usage, thereby reducing the steps necessary to revive effector functions.
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
Christopher D
0000-0001-7716-8504
CD
Scharer
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
Alexander P R
0000-0003-4494-5033
AP
Bally
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322.
Bhanu
0000-0002-4027-1062
B
Gandham
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322 jmboss@emory.edu.
Jeremy M
0000-0002-2432-1840
JM
Boss
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002843:Chromatin / Q000276:immunology*; D042002:Chromatin Assembly and Disassembly; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D019895:Transposases / Q000378:metabolism
D002843:Chromatin; D019895:Transposases