期刊
IMMUNITY
卷 45, 期 2, 页码 333-345出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.07.017
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类别
资金
- NHMRC (Australia)
- ARC Future Fellowship
- NHMRC Practitioner Fellowship
- Queensland Health Research Fellowship
- Australian Post-Graduate Award through University of Queensland, School of Medicine
- NHMRC Senior Research Fellowship
- Singapore's A*STAR
- NRF Singapore [NRF2007NRF-RF001-226]
- Yong Loo Lin School of Medicine, National University of Singapore
- NIH grant [P01 AI56299]
- Medicines for Malaria Venture
Many pathogens, including Plasmodiumspp., exploit the interaction of programmed death-1 (PD-1) with PD-1-ligand-1 (PD-L1) to deactivate'' T cell functions, but the role of PD-L2 remains unclear. We studied malarial infections to understand the contribution of PD-L2 to immunity. Here we have shown that higher PD-L2 expression on blood dendritic cells, from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that PD-L2 was indispensable for establishing effective CD4(+) T cell immunity against malaria, because it not only inhibited PD-L1 to PD-1 activity but also increased CD3 and inducible co-stimulator (ICOS) expression on T cells. Importantly, administration of soluble multimeric PD-L2 to mice with lethal malaria was sufficient to dramatically improve immunity and survival. These studies show immuno-regulation by PD-L2, which has the potential to be translated into an effective treatment for malaria and other diseases where T cell immunity is ineffective or short-lived due to PD-1-mediated signaling.
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