Scientific article
Open access

Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice

Published inScience Translational Medicine, vol. 11, no. 498, eaav5519
Publication date2019

Epidemiological studies associate viral infections during childhood with the risk of developing autoimmune disease during adulthood. However, the mechanistic link between these events remains elusive. We report that transient viral infection of the brain in early life, but not at a later age, precipitates brain autoimmune disease elicited by adoptive transfer of myelin-specific CD4+ T cells at sites of previous infection in adult mice. Early-life infection of mouse brains imprinted a chronic inflammatory signature that consisted of brain-resident memory T cells expressing the chemokine (C-C motif) ligand 5 (CCL5). Blockade of CCL5 signaling via C-C chemokine receptor type 5 prevented the formation of brain lesions in a mouse model of autoimmune disease. In mouse and human brain, CCL5+ TRM were located predominantly to sites of microglial activation. This study uncovers how transient brain viral infections in a critical window in life might leave persisting chemotactic cues and create a long-lived permissive environment for autoimmunity.

  • Animals
  • Antigen-Presenting Cells / immunology
  • Autoimmune Diseases / immunology
  • Brain / immunology
  • Chemokine CCL5 / metabolism
  • Disease Susceptibility
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunologic Memory
  • Lymphocytic choriomeningitis virus / immunology
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • T-Lymphocytes / immunology
Citation (ISO format)
STEINBACH, Karin et al. Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice. In: Science Translational Medicine, 2019, vol. 11, n° 498, p. eaav5519. doi: 10.1126/scitranslmed.aav5519
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Article (Published version)
Article (Accepted version)
Secondary files (4)
ISSN of the journal1946-6234

Technical informations

Creation08/30/2019 2:25:00 PM
First validation08/30/2019 2:25:00 PM
Update time04/11/2023 2:27:00 PM
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