Sepsis impedes EAE disease development and diminishes autoantigen-specific naïve CD4 T cells
- University of Iowa, United States
- University of Minnesota, United States
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
Vladimir P Badovinac
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.
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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Sepsis impedes EAE disease development and diminishes autoantigen-specific naïve CD4 T cells
eLife 9:e55800.
https://doi.org/10.7554/eLife.55800
