Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity

Derek B Danahy; Robert K Strother; Vladimir P Badovinac; Thomas S Griffith

doi:10.1615/CritRevImmunol.2016017098

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Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity

Journal article

Open access

Peer reviewed

Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity

Derek B Danahy, Robert K Strother, Vladimir P Badovinac and Thomas S Griffith

Critical reviews in immunology, Vol.36(1), pp.57-74

2016

DOI: 10.1615/CritRevImmunol.2016017098

PMCID: PMC5314458

PMID: 27480902

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http://doi.org/10.1615/CritRevImmunol.2016017098View

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Abstract

Septic patients experience chronic immunosuppression resulting in enhanced susceptibility to infections normally controlled by T cells. Clinical research on septic patients has shown increased apoptosis and reduced total numbers of CD4 and CD8 T cells, suggesting contributing mechanism driving immunosuppression. Experimental models of sepsis, including cecal ligation and puncture, reverse translated this clinical observation to facilitate hypothesis-driven research and allow the use of an array of experimental tools to probe the impact of sepsis on T-cell immunity. In addition to numerical loss, sepsis functionally impairs the antigen-driven proliferative capacity and effector functions of CD4 and CD8 T cells. Sepsis-induced impairments in both the quantity and quality of T cells results in reduced protective capacity and increased susceptibility of mice to new or previously encountered infections. Therefore, the combined efforts of clinical and experimental sepsis research have begun to elucidate the impact of sepsis on T-cell-mediated immunity and potential T-cell-intrinsic and -extrinsic mechanisms driving chronic immunosuppression. Future work will explore the impact of sepsis on the recently appreciated tissue-resident memory (TRM) T cells, which provide robust protection against localized infections, and dendritic cells, which are needed to activate T cells and promote effective T-cell responses.

Immunity, Cellular - immunology

Sepsis - immunology

Animals

CD8-Positive T-Lymphocytes - immunology

Humans

Details

Title: Subtitle: Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity
Creators: Derek B Danahy - Department of Pathology, University of Iowa, Iowa City, IA; Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA
Robert K Strother - Department of Pathology, University of Iowa, Iowa City, IA
Vladimir P Badovinac - Department of Pathology, Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa
Thomas S Griffith - Department of Urology, University of Minnesota, Minneapolis, MN; Microbiology, Immunology and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN; Center for Immunology, University of Minnesota, Minneapolis, MN; Minneapolis VA Health Care System, Minneapolis, Minnesota
Resource Type: Journal article
Publication Details: Critical reviews in immunology, Vol.36(1), pp.57-74
DOI: 10.1615/CritRevImmunol.2016017098
PMID: 27480902
PMCID: PMC5314458
NLM abbreviation: Crit Rev Immunol
ISSN: 1040-8401
eISSN: 2162-6472
Publisher: United States
Grant note: R01 GM113961 / NIGMS NIH HHS I01 BX001324 / BLRD VA R01 AI114543 / NIAID NIH HHS R21 AI119160 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 2016
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047645902771

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