title: Transcriptional regulation and T cell exhaustion.
abstract: OBJECTIVE
  This review highlights the control of transcriptional networks, including induction of inhibitory receptors, by T cell-specific transcription factors in exhausted T cells that accumulate in chronic viral infections including HIV.
  
  
  RESULTS
  Transcriptional profiling has established distinct molecular phenotypes for exhausted CD4 and CD8 T cells in chronic viral infection models. There exists a subset of transcription factors associated with exhaustion, notably Blimp-1, basic leucine zipper transcription factor, ATF-like and Helios. Epigenetic phenomena are likely important in regulating gene expression networks during exhaustion as illustrated by programmed death 1 promoter methylation patterns.
  
  
  CONCLUSIONS
  Following chronic viral infections, CD4 and CD8 T cells defined functionally and phenotypically as exhausted have distinct transcriptional profiles. These studies have identified a core set of transcription factors that have been implicated in promoting exhaustion. However, no single factor appears to be an exhaustion determining factor, suggesting that T cell exhaustion reflects a combinatorial mechanism with multiple transcription factors interacting to influence the development of functionally exhausted T cells as well as different T effector populations.
authors.affiliation: aDepartment of Medicine bSection of Infectious Diseases, Boston University Medical Center, Boston, Massachusetts, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Collins
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Henderson
mesh_terms: D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors; D059467:Transcriptome
chemical_list: D014157:Transcription Factors