Journal article
Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells
eLife, Vol.9, e55800
11/16/2020
DOI: 10.7554/eLife.55800
PMCID: PMC7721438
PMID: 33191915
Abstract
Evaluation of sepsis-induced immunoparalysis has highlighted how decreased lymphocyte number/function contribute to worsened infection/cancer. Yet, an interesting contrast exists with autoimmune disease development, wherein diminishing pathogenic effectors may benefit the post-septic host. Within this framework, the impact of cecal ligation and puncture (CLP)-induced sepsis on the development of experimental autoimmune encephalomyelitis (EAE) was explored. Notably, CLP mice have delayed onset and reduced disease severity, relative to sham mice. Reduction in disease severity was associated with reduced number, but not function, of autoantigen (MOG)-specific pathogenic CD4 T cells in the CNS during disease and draining lymph node during priming. Numerical deficits of CD4 T cell effectors are associated with the loss of MOG-specific naive precursors. Critically, transfer of MOG-TCR transgenic (2D2) CD4 T cells after, but not before, CLP led to EAE disease equivalent to sham mice. Thus, broad impairment of antigenic responses, including autoantigens, is a hallmark of sepsis-induced immunoparalysis.
Details
- Title: Subtitle
- Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells
- Creators
- Isaac J Jensen - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, United StatesSamantha N Jensen - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, United StatesFrances V Sjaastad - Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, United StatesKatherine N Gibson-Corley - Department of Pathology, University of Iowa, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, United StatesThamothrampillai Dileepan - Department of Microbiology and Immunology, University of Minnesota, Center for Immunology, Minneapolis, United StatesThomas S Griffith - Microbiology, Immunology, and Cancer Biology PhD Program, Department of Urology, Center for Immunology, Minneapolis VA Health Care System, University of Minnesota, Minneapolis, United StatesAshutosh K Mangalam - Interdisciplinary Graduate Program in Immunology, Department of Pathology, University of Iowa, Iowa City, United StatesVladimir P Badovinac - Interdisciplinary Graduate Program in Immunology, Department of Pathology, Department of Microbiology and Immunology, University of Iowa, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.9, e55800
- DOI
- 10.7554/eLife.55800
- PMID
- 33191915
- PMCID
- PMC7721438
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Publisher
- England
- Grant note
- T32CA009138 / NCI NIH HHS P30 ES005605 / NIEHS NIH HHS 1R35134880 / NIGMS NIH HHS R01 AI137075 / NIAID NIH HHS R35 GM134880 / NIGMS NIH HHS 5P30DK054759 / NIDDK NIH HHS AI137075 / National Institute of Allergy and Infectious Diseases AI137075-S1 / National Institute of Allergy and Infectious Diseases I01BX001324 / U.S. Department of Veterans Affairs AI114543 / National Institute of Allergy and Infectious Diseases T32 AI007313 / NIAID NIH HHS T32AI007485 / National Institute of Allergy and Infectious Diseases AI147064 / National Institute of Allergy and Infectious Diseases T32AI007313 / National Institute of Allergy and Infectious Diseases GM113961 / NIGMS NIH HHS T32 AI007485 / NIAID NIH HHS T32AI007511 / National Institute of Allergy and Infectious Diseases GM134880 / NIGMS NIH HHS GM115462 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/16/2020
- Academic Unit
- Microbiology and Immunology; The University of Iowa Institute for Vision Research; Pathology; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070861302771
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