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

Karin Steinbach, Ilena Vincenti, Mario Kreutzfeldt, Nicolas Page, Andreas Muschaweckh, Ingrid Wagner, Ingo Drexler, Daniel Pinschewer, Thomas Korn, Doron Merkler

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

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-γ-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.

Original languageEnglish
Pages (from-to)1571-1587
Number of pages17
JournalJournal of Experimental Medicine
Volume213
Issue number8
DOIs
StatePublished - 25 Jul 2016
Externally publishedYes

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