Targeting metabolism to reverse T-cell exhaustion in chronic viral infections.

Immunology
John D SearsChih-Hao Chang

Abstract

CD8 T-cells are an essential component of the adaptive immune response accountable for the clearance of virus-infected cells via cytotoxic effector functions. Maintaining a specific metabolic profile is necessary for these T-cells to sustain their effector functions and clear pathogens. When CD8 T-cells are activated via T-cell receptor recognition of viral antigen, they transition from a naïve to an effector state and eventually to a memory phenotype, and their metabolic profiles shift as the cells differentiate to accomidate different metabolic demands. However, in the context of particular chronic viral infections (CVIs), CD8 T-cells can become metabolically dysfunctional in a state known as T-cell exhaustion. In this state, CD8 T-cells exhibit reduced effector functions and are unable to properly control pathogens. Clearing these chronic infections becomes progressively difficult as increasing numbers of the effector T-cells become exhausted. Hence, reversal of this dysfunctional metabolic phenotype is vital when considering potential treatments of these infections and offers the opportunity for novel strategies for the development of therapies against CVIs. In this review we explore research implicating alteration of the m...Continue Reading

References

Aug 1, 1991·Current Opinion in Immunology·U H KoszinowskiS Jonjic
Dec 8, 1998·The Journal of Experimental Medicine·M RescignoP Ricciardi-Castagnoli
Jul 18, 2000·European Journal of Immunology·A JossC A Akdis
Mar 13, 2001·Annual Review of Immunology·K W MooreA O'Garra
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heiner WedemeyerBarbara Rehermann
Mar 12, 2004·The New England Journal of Medicine·Don Ganem, Alfred M Prince
Sep 22, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hans Christian SpangenbergRobert Thimme
Oct 22, 2005·Nature Reviews. Immunology·Casey J FoxCraig B Thompson
Oct 13, 2006·The Journal of Experimental Medicine·Mette EjrnaesMatthias G von Herrath
Oct 17, 2006·Nature Medicine·David G BrooksMichael B A Oldstone
Mar 6, 2007·Trends in Microbiology·Shawn D Blackburn, E John Wherry
Jun 16, 2007·BMC Immunology·Charles H MarisJoshy Jacob
Sep 27, 2008·Journal of Leukocyte Biology·Bisheng LiuAndre Boonstra
Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael J MolloyEdward J Usherwood
May 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Scott N Mueller, Rafi Ahmed
Jun 6, 2009·Nature·Erika L PearceYongwon Choi
Jun 23, 2009·Nature·Koichi ArakiRafi Ahmed
Mar 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah R JacobsJeffrey C Rathmell
Jul 9, 2011·Nature Immunology·E John Wherry
Dec 31, 2011·Immunity·Gerritje J W van der WindtErika L Pearce
Aug 15, 2012·Immunological Reviews·Gerritje J W van der Windt, Erika L Pearce
Dec 3, 2013·Advances in Physiology Education·Nathan D PennockRoss M Kedl
Feb 22, 2014·Current Opinion in Immunology·Jason A MaciolekHeather L Wilson
May 6, 2014·Frontiers in Immunology·Sietske Rosendahl HuberDebbie van Baarle
Jan 27, 2015·Virology·Shannon M KahanAllan J Zajac
Mar 11, 2015·Retrovirology·Vijayakumar VeluEsaki M Shankar

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Citations

Jan 15, 2021·Immunology·Eyal Amiel, Georgia Perona-Wright
Feb 7, 2021·Molecular Cancer·Longzheng XiaQianjin Liao
Jun 9, 2021·Reproductive Sciences·Dan LiYeling Wang

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