Journal
IMMUNITY
Volume 45, Issue 4, Pages 889-902Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2016.08.011
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Funding
- National Health and Medical Research Council of Australia
- Australian Research Council
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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 tissueresident 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 Trmcells and provides approaches for their selective transfer, expansion, ordepletion, whichmay be harnessed to control liver infections or autoimmunity.
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