Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection

Steinbach, K. and Vincenti, I. and Kreutzfeldt, M. and Page, N. and Muschaweckh, A. and Wagner, I. and Drexler, I. and Pinschewer, D. and Korn, T. and Merkler, D.. (2016) Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection. J Exp Med, 213 (8). pp. 1571-1587.

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Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8(+) memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-gamma-dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity.
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
ISSN:1540-9538 (Electronic) 0022-1007 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 May 2020 08:06
Deposited On:25 May 2020 08:06

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