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Review
. 2021 Sep 23;17(9):e1009892.
doi: 10.1371/journal.ppat.1009892. eCollection 2021 Sep.

Immunological exhaustion: How to make a disparate concept operational?

Hannah Kaminski  1 , Maël Lemoine  1 , Thomas Pradeu  1
Affiliations
Review

Immunological exhaustion: How to make a disparate concept operational?

Hannah Kaminski et al. PLoS Pathog. .

Abstract

In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as to make the concept of exhaustion genuinely operational.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Three different approaches to immunological exhaustion.
These approaches use different criteria and do not always overlap.
Fig 2
Fig 2. Key controversies about immunological “exhaustion”.
COVID-19, Coronavirus Disease 2019; HBV, hepatitis B virus; HCV, hepatitis C virus; IL, interleukin; LCMV, lymphocytic choriomeningitis virus; TGF-β, transforming growth factor beta; Tumor Micro Environment (TME), xxx.
Fig 3
Fig 3. Targeting “exhaustion” in cancer therapies means different things depending on the approach to immunological exhaustion one adopts.
PD-1, programmed cell death protein 1.
Fig 4
Fig 4. Examples of absence of overlap between the 3 approaches to exhaustion.
COVID, Coronavirus Disease; HBV, hepatitis B virus; HCV, hepatitis C virus; LCMV, lymphocytic choriomeningitis virus.
See this image and copyright information in PMC

References

    1. Byers VS, Sercarz EE. The X-Y-Z scheme of immunocyte maturation. IV. The exhaustion of memory cells. J Exp Med. 1968;127:307–25. doi: 10.1084/jem.127.2.307 - DOI - PMC - PubMed
    1. Byers VS, Sercarz EE. The X-Y-Z scheme of immunocyte maturation. V. Paralysis of memory cells. J Exp Med. 1968;128:715–28. doi: 10.1084/jem.128.4.715 - DOI - PMC - PubMed
    1. Moskophidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature. 1993;362:758–61. doi: 10.1038/362758a0 - DOI - PubMed
    1. Gallimore A, Glithero A, Godkin A, Tissot AC, Plückthun A, Elliott T, et al.. Induction and Exhaustion of Lymphocytic Choriomeningitis Virus–specific Cytotoxic T Lymphocytes Visualized Using Soluble Tetrameric Major Histocompatibility Complex Class I–Peptide Complexes. J Exp Med. 1998;187:1383–93. doi: 10.1084/jem.187.9.1383 - DOI - PMC - PubMed
    1. Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJD, Suresh M, Altman JD, et al.. Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function. J Exp Med. 1998;188:2205–13. doi: 10.1084/jem.188.12.2205 - DOI - PMC - PubMed

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