Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory

Immunity. 2012 Dec 14;37(6):1130-44. doi: 10.1016/j.immuni.2012.08.021. Epub 2012 Nov 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Chronic Disease
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Immunologic Memory / genetics*
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription, Genetic


  • Transcription Factors