Format

Send to

Choose Destination
Immunity. 2016 Oct 18;45(4):889-902. doi: 10.1016/j.immuni.2016.08.011. Epub 2016 Sep 27.

Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection.

Author information

1
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia.
2
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia; Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, VIC 3004, Australia.
3
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia; The ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC 3010, Australia.
4
Liver Immunology Program, Centenary Institute and AW Morrow Gastroenterology and Liver Centre, University of Sydney and Royal Prince Alfred Hospital, Locked Bag No 6, Sydney, NSW 2042, Australia.
5
The School of BioSciences, University of Melbourne, Parkville, VIC 3010, Australia.
6
Department of Electrical and Electronic Engineering, The University of Melbourne, Parkville, VIC 3010, Australia.
7
Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, VIC 3004, Australia; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3168, Australia.
8
Institute of Immunology, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
9
Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, VIC 3004, Australia.
10
Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
11
Macfarlane Burnet Institute for Medical Research & Public Health, Melbourne, VIC 3004, Australia; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3168, Australia. Electronic address: irina.caminschi@monash.edu.au.
12
Department of Microbiology and Immunology, The Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia; The ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: wrheath@unimelb.edu.au.

Abstract

In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8+ T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids. Exploring the requirements for liver Trm cell induction, we showed that by combining dendritic cell-targeted priming with liver inflammation and antigen recognition on hepatocytes, high frequencies of Trm cells could be induced and these cells were essential for protection against malaria sporozoite challenge. Our study highlights the immune potential of liver Trm cells and provides approaches for their selective transfer, expansion, or depletion, which may be harnessed to control liver infections or autoimmunity.

KEYWORDS:

CD8(+) T cells; Clec9A; liver; liver surveillance; malaria; memory T cells; sporozoite; tissue-resident memory; vaccine

PMID:
27692609
DOI:
10.1016/j.immuni.2016.08.011
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center