Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Ave., Wooster, OH 44691, USA.
J Clin Immunol. 2011 Apr;31(2):228-39. doi: 10.1007/s10875-010-9476-4. Epub 2010 Nov 2.
Important roles played by invariant natural killer T (iNKT) cells in asthma pathogenesis have been demonstrated. We identified functional iNKT cells and CD1d molecules in pig lungs. Pig iNKT cells cultured in the presence of α-GalCer proliferated and secreted Th1 and Th2 cytokines. Like in other animal models, direct activation of pig lung iNKT cells using α-GalCer resulted in acute airway hyperreactivity (AHR). Clinically, acute AHR-induced pigs had increased respiratory rate, enhanced mucus secretion in the airways, fever, etc. In addition, we observed petechial hemorrhages, infiltration of CD4(+) cells, and increased Th2 cytokines in AHR-induced pig lungs. Ex vivo proliferated iNKT cells of asthma induced pigs in the presence of C-glycoside analogs of α-GalCer had predominant Th2 phenotype and secreted more of Th2 cytokine, IL-4. Thus, baby pigs may serve as a useful animal model to study iNKT cell-mediated AHR caused by various environmental and microbial CD1d-specific glycolipid antigens.
已证实不变自然杀伤 T(iNKT)细胞在哮喘发病机制中发挥重要作用。我们在猪肺中鉴定出功能性 iNKT 细胞和 CD1d 分子。在 α-GalCer 存在的情况下培养的猪 iNKT 细胞增殖并分泌 Th1 和 Th2 细胞因子。与其他动物模型一样，使用 α-GalCer 直接激活猪肺 iNKT 细胞会导致急性气道高反应性(AHR)。临床上，急性 AHR 诱导的猪呼吸频率增加，气道内黏液分泌增加，发热等。此外，我们观察到 AHR 诱导的猪肺中有瘀点样出血、CD4+细胞浸润和 Th2 细胞因子增加。在 C-糖苷类似物 α-GalCer 的存在下，哮喘诱导的猪离体增殖的 iNKT 细胞具有明显的 Th2 表型，并分泌更多的 Th2 细胞因子 IL-4。因此，仔猪可能成为研究各种环境和微生物 CD1d 特异性糖脂抗原引起的 iNKT 细胞介导的 AHR 的有用动物模型。
