1. Immunology and Inflammation
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Sepsis impedes EAE disease development and diminishes autoantigen-specific naïve CD4 T cells

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Cite this article as: eLife 2020;9:e55800 doi: 10.7554/eLife.55800

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided.

Article and author information

Author details

  1. Isaac J jensen

    Pathology, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Samantha N Jensen

    Pathology, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Frances V Sjaastad

    Department of Pharmacology, Center for Immunology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Katherine N Gibson-Corley

    Pathology, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Thamothrampillai Dileepan

    Microbiology and Immunology, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Thomas S Griffith

    Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7205-9859
  7. Ashutosh K Mangalam

    Pathology, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Vladimir P Badovinac

    Pathology, University of Iowa, Iowa City, United States
    For correspondence
    vladimir-badovinac@uiowa.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3180-2439

Funding

National Institute of Allergy and Infectious Diseases (AI114543)

  • Vladimir P Badovinac

National Institute of Allergy and Infectious Diseases (T32AI007511)

  • Isaac J jensen

National Institute of Allergy and Infectious Diseases (T32AI007485)

  • Isaac J jensen

National Institute of Allergy and Infectious Diseases (T32AI007485)

  • Samantha N Jensen

National Institute of Allergy and Infectious Diseases (AI137075-S1)

  • Samantha N Jensen

National Cancer Institute (T32CA009138)

  • Frances V Sjaastad

National Institute of Allergy and Infectious Diseases (T32AI007313)

  • Frances V Sjaastad

National Institute of General Medical Sciences (1R35134880)

  • Vladimir P Badovinac

National Institute of Allergy and Infectious Diseases (AI147064)

  • Vladimir P Badovinac

National Institute of General Medical Sciences (GM113961)

  • Vladimir P Badovinac

National Institute of General Medical Sciences (GM134880)

  • Vladimir P Badovinac

National Institute of General Medical Sciences (GM115462)

  • Thomas S Griffith

National Institute of Allergy and Infectious Diseases (AI137075)

  • Ashutosh K Mangalam

U.S. Department of Veterans Affairs (I01BX001324)

  • Thomas S Griffith

National Institute of Environmental Health Sciences (P30 ES005605)

  • Katherine N Gibson-Corley
  • Ashutosh K Mangalam

National Institute of Diabetes and Digestive and Kidney Diseases (5P30DK054759)

  • Katherine N Gibson-Corley

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experimental procedures using mice were approved by University of Iowa Animal Care and Use Committee under ACURF protocol number 9101915. The experiments performed followed Office of Laboratory Animal Welfare guidlines and PHS policy on Humane Care and Use of Laboratory Animals. Euthansia was performed by cervical dislocation or carbon dioxide asphyxiation.

Reviewing Editor

  1. Urszula Krzych, Walter Reed Army Institute of Research, United States

Publication history

  1. Received: February 6, 2020
  2. Accepted: November 15, 2020
  3. Accepted Manuscript published: November 16, 2020 (version 1)
  4. Version of Record published: December 7, 2020 (version 2)

Copyright

© 2020, jensen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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