Characterizing porcine invariant natural killer T cells: A comparative study with NK cells and T cells

CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells that share phenotypic characteristics of both NK and conventional T cells (Tconv). Although iNKT cells have been well characterized in mice and humans, functional CD1d and CD1d-restricted iNKT cells are not universally expressed in mammals. Swine express iNKT cells that can be detected using α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. In the present study, we characterized iNKT cells from the blood, spleen, lymph node, lung and liver of commercial mixed-breed pigs, and compared their phenotype to NK cells and Tconv. The principal findings are that pig iNKT cells are CD8α and CD44 positive and CD11b and Nkp46 negative. Most are also negative for the CD4 co-receptor, which is used to distinguish functionally distinct mouse and human iNKT cells subsets. The frequency of IFN-γ-producing CD8α^bright iNKT cells was 3-4-fold higher than CD8α^dull iNKT cells, suggesting that CD8α expression identifies iNKT cells with a unique functional role in immune responses. Finally, large variability was detected among pigs in interactions between iNKT cells and monocytes when iNKT cells were activated with α-GalCer, which raises a cautionary note about manipulating iNKT cells for immunotherapy. Collectively, our study provides important phenotypic and functional information about porcine iNKT cells that will be useful for understanding how iNKT cells contribute to immune responses in swine, with potential implications for human health.