TY - JOUR TI - 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 A2 - Krzych, Urszula A2 - Rath, Satyajit A2 - Kuman, Pawn A2 - Casares, Sofia VL - 9 PY - 2020 DA - 2020/11/16 SP - e55800 C1 - eLife 2020;9:e55800 DO - 10.7554/eLife.55800 UR - https://doi.org/10.7554/eLife.55800 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. KW - sepsis KW - EAE KW - CD4 T cells KW - immunoparalysis KW - adoptive transfer JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -