Sepsis impedes EAE disease development and diminishes autoantigen-specific naive CD4 T cells.

Autor:	Jensen IJ; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, United States., Jensen SN; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, United States., Sjaastad FV; Microbiology, Immunology, and Cancer Biology PhD Program, University of Minnesota, Minneapolis, United States., Gibson-Corley KN; Department of Pathology, University of Iowa, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, United States., Dileepan T; Department of Microbiology and Immunology, University of Minnesota, Center for Immunology, Minneapolis, United States., Griffith TS; Microbiology, Immunology, and Cancer Biology PhD Program, Department of Urology, Center for Immunology, Minneapolis VA Health Care System, University of Minnesota, Minneapolis, United States., Mangalam AK; Interdisciplinary Graduate Program in Immunology, Department of Pathology, University of Iowa, Iowa City, United States., Badovinac VP; Interdisciplinary Graduate Program in Immunology, Department of Pathology, Department of Microbiology and Immunology, University of Iowa, Iowa City, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Nov 16; Vol. 9. Date of Electronic Publication: 2020 Nov 16.
DOI:	10.7554/eLife.55800
Abstrakt:	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. Competing Interests: IJ, SJ, FS, KG, TD, TG, AM, VB No competing interests declared (© 2020, Jensen et al.)
Databáze:	MEDLINE
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