@article {542116,
	title = {Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection.},
	journal = {PLoS One},
	volume = {8},
	number = {3},
	year = {2013},
	month = {2013},
	pages = {e59599},
	abstract = {There is evidence indicating that invariant Natural Killer T (iNKT) cells play an important role in defense against influenza A virus (IAV). However, the effect of inhibitory receptor, programmed death-1 (PD-1), and its ligands, programmed death ligand (PD-L) 1 and 2 on iNKT cells in protection against IAV remains to be elucidated. Here we investigated the effects of these co-stimulatory molecules on iNKT cells in the response to influenza. We discovered that compare to the wild type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident by reduced weight loss, decreased pulmonary inflammation and cellular infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss, pulmonary inflammation and cellular infiltration compare to the wild type mice after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1 or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these findings. Interestingly, in our transfer system PD-L1(-/-)-derived iNKT cells produced high levels of interferon-gamma whereas PD-L2(-/-)-derived iNKT cells produced high amounts of interleukin-4 and 13 suggesting a role for these cytokines in sensitivity to influenza. We identified that PD-L1 negatively regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice. Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells reduces the sensitivity to IAV and that the presence of PD-L2 is important for dampening the deleterious inflammatory responses after IAV infection. Our findings potentially have clinical implications for developing new therapies for influenza.},
	keywords = {Animals, Antigens, CD274, Cytokines, Dendritic Cells, Female, Gene Expression Regulation, Gene Knockout Techniques, Influenza A Virus, H1N1 Subtype, Lung, Mice, Mice, Inbred BALB C, Natural Killer T-Cells, Orthomyxoviridae Infections, Programmed Cell Death 1 Ligand 2 Protein},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0059599},
	author = {Maazi, Hadi and Singh, Abinav K and Speak, Anneliese O and Lombardi, Vincent and Lam, Jonathan and Khoo, Bryant and Inn, Kyung Soo and Sharpe, Arlene H and Jung, Jae U and Akbari, Omid}
}
