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

Steinbach, Karin and Vincenti, Ilena and Egervari, Kristof and Kreutzfeldt, Mario and van der Meer, Franziska and Page, Nicolas and Klimek, Bogna and Rossitto-Borlat, Irène and Di Liberto, Giovanni and Muschaweckh, Andreas and Wagner, Ingrid and Hammad, Karim and Stadelmann, Christine and Korn, Thomas and Hartley, Oliver and Pinschewer, Daniel D. and Merkler, Doron. (2019) Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice. Science translational medicine, 11 (498). eaav5519.

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Official URL: https://edoc.unibas.ch/76553/

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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; +; T; RM; 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 May 2020 08:03
Deposited On:21 May 2020 08:03

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