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Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells
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 th...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721438/ https://www.ncbi.nlm.nih.gov/pubmed/33191915 http://dx.doi.org/10.7554/eLife.55800 |
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author | Jensen, Isaac J Jensen, Samantha N Sjaastad, Frances V Gibson-Corley, Katherine N Dileepan, Thamothrampillai Griffith, Thomas S Mangalam, Ashutosh K Badovinac, Vladimir P |
author_facet | Jensen, Isaac J Jensen, Samantha N Sjaastad, Frances V Gibson-Corley, Katherine N Dileepan, Thamothrampillai Griffith, Thomas S Mangalam, Ashutosh K Badovinac, Vladimir P |
author_sort | Jensen, Isaac J |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7721438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77214382020-12-09 Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells Jensen, Isaac J Jensen, Samantha N Sjaastad, Frances V Gibson-Corley, Katherine N Dileepan, Thamothrampillai Griffith, Thomas S Mangalam, Ashutosh K Badovinac, Vladimir P eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2020-11-16 /pmc/articles/PMC7721438/ /pubmed/33191915 http://dx.doi.org/10.7554/eLife.55800 Text en © 2020, Jensen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Jensen, Isaac J Jensen, Samantha N Sjaastad, Frances V Gibson-Corley, Katherine N Dileepan, Thamothrampillai Griffith, Thomas S Mangalam, Ashutosh K Badovinac, Vladimir P Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
title | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
title_full | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
title_fullStr | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
title_full_unstemmed | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
title_short | Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells |
title_sort | sepsis impedes eae disease development and diminishes autoantigen-specific naive cd4 t cells |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721438/ https://www.ncbi.nlm.nih.gov/pubmed/33191915 http://dx.doi.org/10.7554/eLife.55800 |
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