Deshapriya S Karunarathne, Joshua M Horne-Debets, Johnny X Huang, Rebecca Faleiro, Chiuan Yee Leow, Fiona Amante, Thomas S Watkins, John J Miles, Patrick J Dwyer, Katryn J Stacey, Michael Yarski, Chek Meng Poh, Jason S Lee, Matthew A Cooper, Laurent Rénia, Derek Richard, James S McCarthy, Arlene H Sharpe, Michelle N Wykes
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...
August 16, 2016: Immunity