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Current Opinion in HIV & AIDS:
doi: 10.1097/COH.0000000000000091
CELL EXHAUSTION IN HIV-1 INFECTION: Edited by Daniel E. Kaufmann and Nabila Seddiki

Transcriptional regulation and T cell exhaustion

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

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Abstract

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.

© 2014 Lippincott Williams & Wilkins, Inc.

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