TY - JOUR
T1 - Sepsis impedes eae disease development and diminishes autoantigen-specific naive cd4 t cells
AU - Jensen, Isaac J.
AU - Jensen, Samantha N.
AU - Sjaastad, Frances V.
AU - Gibson-Corley, Katherine N.
AU - Dileepan, Thamothrampillai
AU - Griffith, Thomas S.
AU - Mangalam, Ashutosh K.
AU - Badovinac, Vladimir P.
N1 - Publisher Copyright:
© Jensen et al.
PY - 2020/11/16
Y1 - 2020/11/16
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.55800
DO - 10.7554/eLife.55800
M3 - Article
C2 - 33191915
AN - SCOPUS:85097542178
SN - 2050-084X
VL - 9
SP - 1
EP - 24
JO - eLife
JF - eLife
M1 - e55800
ER -