TY - JOUR
T1 - Network Analysis Reveals Centrally Connected Genes and Pathways Involved in CD8+ T Cell Exhaustion versus Memory
AU - Doering, Travis A.
AU - Crawford, Alison
AU - Angelosanto, Jill M.
AU - Paley, Michael A.
AU - Ziegler, Carly G.
AU - Wherry, E. John
N1 - Funding Information:
We thank the Wherry laboratory for helpful suggestions and feedback. We also thank Avinash Bhandoola, Mark Siracusa, and Michael Abt for comments and input. This work was supported by the National Institutes of Health (AI082630, AI083022, AI078897, and HHSN266200500030C to E.J.W.) and the Dana Foundation (E.J.W). E.J.W. has a patent licensing agreement on the PD-1 pathway.
PY - 2012/12/14
Y1 - 2012/12/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870922385&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.08.021
DO - 10.1016/j.immuni.2012.08.021
M3 - Article
C2 - 23159438
AN - SCOPUS:84870922385
SN - 1074-7613
VL - 37
SP - 1130
EP - 1144
JO - Immunity
JF - Immunity
IS - 6
ER -