Title:NKT Cell Subsets Can Exert Opposing Effects in Autoimmunity, Tumor Surveillance and Inflammation
Volume: 8
Issue: 4
Author(s): Rachael Viale, Randle Ware, Igor Maricic, Varun Chaturvedi and Vipin Kumar
Affiliation:
Keywords:
CD1, cancer, glycolipids, NKT cells, sulfatide, Th1/Th17
Abstract: The innate-like natural killer T (NKT) cells are essential regulators of immunity. These cells comprise at least
two distinct subsets and recognize different lipid antigens presented by the MHC class I like molecules CD1d. The CD1ddependent
recognition pathway of NKT cells is highly conserved from mouse to humans. While most type I NKT cells
can recognize αGalCer and express a semi-invariant T cell receptor (TCR), a major population of type II NKT cells
reactive to sulfatide utilizes an oligoclonal TCR. Furthermore TCR recognition features of NKT subsets are also
distinctive with almost parallel as opposed to perpendicular footprints on the CD1d molecules for the type I and type II
NKT cells respectively. Here we present a view based upon the recent studies in different clinical and experimental
settings that while type I NKT cells are more often pathogenic, they may also be regulatory. On the other hand, sulfatidereactive
type II NKT cells mostly play an inhibitory role in the control of autoimmune and inflammatory diseases. Since
the activity and cytokine secretion profiles of NKT cell subsets can be modulated differently by lipid ligands or their
analogs, novel immunotherapeutic strategies are being developed for their differential activation for potential intervention
in inflammatory diseases.
