Porcine natural killer T cells

Invariant natural killer T (iNKT) cells are a subset of so-called innate-like T cells that share phenotypic characteristics of both NK and conventional T cells. Unlike conventional T cells, iNKT cells express a semi-invariant T cell receptor (TCR) (TRAV10-TRAJ18/TRBV25-1 in humans and TRAV11-TRAJ18/TRBV13, TRBV29, or TRBV1 in mice) that dictates their antigen specificity. iNKT cells recognize glycolipid antigens such as a-galctosylceramide (a-GalCer) presented by the non-polymorphic major histocompatibility complex (MHC) class I-like molecule, CD1d. Once activated, they interact with and influence multiple cell types in both innate and adaptive immune systems. Immune responses induced by activated iNKT cells resemble conventional CD4(+) T helper cells in many aspects. Therefore, these cells have been studied extensively particularly for their therapeutic potential to treat various infectious and inflammatory diseases, autoimmune diseases, and cancer. However, the majority of this research has employed mouse studies that have been difficult to translate into humans due in part to differences in iNKT cells between mice and humans. Although iNKT cells have been well characterized in mice and humans, very little is known about these cells in pigs. Like human and mouse iNKT cells, porcine iNKT cells possess a memory/activation phenotype, indicated by high MHC IISLA-DR and CD5, and low CD45RA expression. Our previous studies have characterized the phenotype, function, and TCR repertoire diversity of iNKT cells in healthy pigs. Our results show that pig and human iNKT cells are fundamentally similar for their frequency, distribution, and TCR repertoire diversity, which suggests that iNKT cells between these species play a similar role in immunity and disease. We further evaluated the adjuvant effects of iNKT cells on swine influenza vaccines and showed that alpha-GalCer-elicited immune responses improved influenza vaccine efficacy. Our findings also indicate that pigs offer a valuable preclinical model for understanding how iNKT cells contribute to influenza infections in humans. Swine hold several advantages over mice as a preclinical model for iNKT cell therapy because of the many similarities between human and pig iNKT cells. In this review, we first briefly summarize the activation modes and immunoregulatory functions of iNKT cells. Then we compare the phenotype and tissue distribution of porcine iNKT cells, focusing on their similarities and differences to their counterparts in mice and humans. Lastly, we review the adjuvant effects of iNKT cell agonists and discuss some challenges that must be overcome before iNKT cell agonists can be contemplated for veterinary use in livestock.