Research ArticleAutoimmunity

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

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Science Translational Medicine  26 Jun 2019:
Vol. 11, Issue 498, eaav5519
DOI: 10.1126/scitranslmed.aav5519

Autoimmunity goes viral

The etiology of most autoimmune disorders remains unknown. Viral infection has been associated with the risk of developing autoimmune diseases; however, a precise causal relationship has yet to be identified. Steinbach et al. now show that transient brain viral infection early in life worsened lesion development and symptoms in a mouse model of autoimmune disease. Autoimmune lesions were spatially associated with areas of previous viral infection in mice. Mechanistically, early-life viral infection induced a persistent population of chemokine ligand 5 (CCL5)–expressing brain-resident memory T cells that promoted a long-lasting proinflammatory environment. Blockade of CCL5 signaling prevented the increased predisposition to autoimmunity in the mouse model.


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.

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