%0 Journal Article %J PLoS One %D 2013 %T Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection. %A Maazi, Hadi %A Singh, Abinav K %A Speak, Anneliese O %A Lombardi, Vincent %A Lam, Jonathan %A Khoo, Bryant %A Inn, Kyung Soo %A Sharpe, Arlene H %A Jung, Jae U %A Akbari, Omid %K Animals %K Antigens, CD274 %K Cytokines %K Dendritic Cells %K Female %K Gene Expression Regulation %K Gene Knockout Techniques %K Influenza A Virus, H1N1 Subtype %K Lung %K Mice %K Mice, Inbred BALB C %K Natural Killer T-Cells %K Orthomyxoviridae Infections %K Programmed Cell Death 1 Ligand 2 Protein %X 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. %B PLoS One %V 8 %P e59599 %8 2013 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/23555047?dopt=Abstract %R 10.1371/journal.pone.0059599