有证据表明不变的自然杀伤T（iNKT）细胞在防护对抗A型流感病毒中发挥重要的作用。然而，抑制受体，程序性死亡因子1（PD1）及其配体，程序性死亡配体（PK-L）1和2在iNKT细胞上防护对抗A型流感病毒中的作用被证实。研究人员调查了在iNKT细胞上的这些共刺激分子的对流行性感冒的效应。  文中研究结果证明iNKT细胞减少了对IAV的敏感性导致PK-L1表达的缺乏，并且在IAV后PD-L2是抑制有害炎症应答中PD-L2的存在具有重要作用。 原文摘要： Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection Hadi Maazi,Abinav K. Singh,Anneliese O. Speak,Vincent Lombardi,Jonathan Lam,Bryant Khoo,Kyung Soo Inn,Arlene H. Sharpe,Jae U. Jung,Omid Akbari 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. |
