Invariant NKT cells in pig lung: a potential asthma model (141.8)

Abstract

Abstract Biomedical research in pigs is critical for better human health, as they are immunologically and physiologically more similar to humans, and are an excellent animal model to alleviate human asthma. Natural Killer T (NKT) cells with an invariant TCR are called "invariant NKT" (iNKT). iNKT cells are activated by CD1d-bound glycolipids with a unique α-anomerically linked sugar (e.g. α-GalCer). For the first time in pigs, we detected iNKT cells and CD1d expression. The pig iNKT cells proliferated and secreted both Th1 and Th2 cytokines when cultured in the presence of α-GalCer. In particular, iNKT cells from lung, and lung draining lymph nodes proliferated to higher numbers (<1% to >30%), with the secretion of more cytokines, compared to iNKT cells from other tissues. Recently, “many pivotal roles” played by iNKT cells in asthma pathogenesis have been reported. Direct activation of pig lung iNKT cells using α-GalCer resulted in airway hyperreactivity (AHR), and clinically those pigs had dyspnea with elevated body temperature. The AHR induced pig lung had petechial hemorrhages with increased mucus secretion in the airway. The α-GalCer received pigs had three-fold increase in cytokines, IL-6, IL-12 and IL-10, and two-fold increase in CD1d expression on the dendritic cells and macrophages at post-24 of inoculation. A moderate increase in iNKT cells in lungs of AHR induced pigs was also detected, compared to controls. This work is supported by USDA and NPB grants to RJG.