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Critical Reviews™ in Immunology
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ISSN Druckformat: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2016017098
pages 57-74

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

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

ABSTRAKT

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.


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