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Transcriptional regulation and T cell exhaustion

Collins, Matthew H.a; Henderson, Andrew J.a,b

Current Opinion in HIV and AIDS: September 2014 - Volume 9 - Issue 5 - p 459–463
doi: 10.1097/COH.0000000000000091
CELL EXHAUSTION IN HIV-1 INFECTION: Edited by Daniel E. Kaufmann and Nabila Seddiki
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Purpose of review 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.

Recent findings 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.

Summary 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.

aDepartment of Medicine

bSection of Infectious Diseases, Boston University Medical Center, Boston, Massachusetts, USA

Correspondence to Andrew J. Henderson, Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, MA 02118, USA. Tel: +1 617 414 5240; e-mail:

© 2014 Lippincott Williams & Wilkins, Inc.