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J Exp Med. 2016 Jul 25;213(8):1571-87. doi: 10.1084/jem.20151916. Epub 2016 Jul 4.

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

Author information

1
Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland.
2
Klinikum rechts der Isar, Department of Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany.
3
Institute of Virology, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
4
Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.
5
Klinikum rechts der Isar, Department of Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany.
6
Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland Division of Clinical Pathology, Geneva University Hospital, 1211 Geneva, Switzerland doron.merkler@unige.ch.

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.

PMID:
27377586
PMCID:
PMC4986533
DOI:
10.1084/jem.20151916
[Indexed for MEDLINE]
Free PMC Article

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