Sepsis impedes eae disease development and diminishes autoantigen-specific naive cd4 t cells

Isaac J. Jensen, Samantha N. Jensen, Frances V. Sjaastad, Katherine N. Gibson-Corley, Thamothrampillai Dileepan, Thomas S. Griffith, Ashutosh K. Mangalam, Vladimir P. Badovinac

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere55800
Pages (from-to)1-24
Number of pages24
JournaleLife
Volume9
DOIs
StatePublished - Nov 16 2020

Bibliographical note

Publisher Copyright:
© Jensen et al.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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