Programmed death-1 ligand 2-mediated regulation of the PD-L1 to PD-1 axis is essential for establishing CD4+ T cell immunity

Karunarathne, Deshapriya S., Horne-Debets, Joshua M., Huang, Johnny X., Faleiro, Rebecca, Leow, Chiuan Yee, Amante, Fiona, Watkins, Thomas S., Miles, John J., Dwyer, Patrick J., Stacey, Katryn J., Yarski, Michael, Poh, Chek Meng, Lee, Jason S., Cooper, Matthew A., Rénia, Laurent, Richard, Derek, McCarthy, James S., Sharpe, Arlene H. and Wykes, Michelle N. (2016) Programmed death-1 ligand 2-mediated regulation of the PD-L1 to PD-1 axis is essential for establishing CD4+ T cell immunity. Immunity, 45 2: 333-345. doi:10.1016/j.immuni.2016.07.017


Author Karunarathne, Deshapriya S.
Horne-Debets, Joshua M.
Huang, Johnny X.
Faleiro, Rebecca
Leow, Chiuan Yee
Amante, Fiona
Watkins, Thomas S.
Miles, John J.
Dwyer, Patrick J.
Stacey, Katryn J.
Yarski, Michael
Poh, Chek Meng
Lee, Jason S.
Cooper, Matthew A.
Rénia, Laurent
Richard, Derek
McCarthy, James S.
Sharpe, Arlene H.
Wykes, Michelle N.
Title Programmed death-1 ligand 2-mediated regulation of the PD-L1 to PD-1 axis is essential for establishing CD4+ T cell immunity
Formatted title
Programmed death-1 ligand 2-mediated regulation of the PD-L1 to PD-1 axis is essential for establishing CD4+ T cell immunity
Journal name Immunity   Check publisher's open access policy
ISSN 1074-7613
1097-4180
Publication date 2016-08-16
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.immuni.2016.07.017
Open Access Status Not yet assessed
Volume 45
Issue 2
Start page 333
End page 345
Total pages 13
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
Many pathogens, including Plasmodium spp., 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.
Keyword Plasmodium
Malarial infections
Malaria
CD4+ T cell immunity
Programmed death-1 (PD-1)
PD-1-ligand-1 (PD-L1)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 19 Aug 2016, 20:14:12 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences