title: Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory.
abstract: Exhausted CD8(+) T cells function poorly and are negatively regulated by inhibitory receptors. Transcriptional profiling has identified gene expression changes associated with exhaustion. However, the transcriptional pathways critical to the differences between exhausted and functional memory CD8(+) T cells are unclear. We thus defined transcriptional coexpression networks to define pathways centrally involved in exhaustion versus memory. These studies revealed differences between exhausted and memory CD8(+) T cells including the following: lack of coordinated transcriptional modules of quiescence during exhaustion, centrally connected hub genes, pathways such as transcription factors, genes involved in regulation of immune responses, and DNA repair genes, as well as differential connectivity for genes including T-bet, Eomes, and other transcription factors. These data identify pathways involved in CD8(+) T cell exhaustion, and highlight the context-dependent nature of transcription factors in exhaustion versus memory.
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Doering
authors.forename: Alison
authors.initials: A
authors.lastname: Crawford
authors.forename: Jill M
authors.initials: JM
authors.lastname: Angelosanto
authors.forename: Michael A
authors.initials: MA
authors.lastname: Paley
authors.forename: Carly G
authors.initials: CG
authors.lastname: Ziegler
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
mesh_terms: D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002908:Chronic Disease; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007156:Immunologic Memory / Q000235:genetics*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors