Work

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

Year: 2020

Type: article

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.

Source: eLife

DOI: 10.7554/elife.55800

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

Institutions: University of Iowa, University of Minnesota, University of Iowa Hospitals and Clinics, University of Iowa Holden Comprehensive Cancer Center, Minneapolis VA Health Care System

Language: English

Topic: Multiple Sclerosis Research Studies

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500

Funders: U.S. Department of Veterans Affairs, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences

Awards: G1296717744, G1419578588, G1973313420, G2402583483, Differentiation of pathogen-specific memory CD8 T cell responses, G3554579951, Cellular and molecular mechanisms controlling sepsis-induced immunoparalyses state, G4582172752, Impairment and recovery of CD8 T cell responses after sepsis, Linking diet, gut microbiota and autoimmune disease: Bacteria induced phytoestrogen metabolites impact immune function in Experimental Autoimmune Encephalitis, Memory CD8 T cell localization and protection from influenza, G701660491, G7049798106, Alterations in CD4 T cells during sepsis, G9000010685, Environmental Health Sciences Research Center, Training in Mechanisms of Parasitism, Immunology Training Program, Molecular, Genetic and Cellular Targets of Cancer Training Program, Predoctoral Training Program in Immunology, Precision Medicine Center for Cystic Fibrosis

OpenAlex ID: W3102377859

FWCI: 2.462

Cites: 71

Cited by: 26

Related to: 10