CD1d-Restricted Natural Killer T Cells: Roles in Tumor Immunosurveillance and Tolerance

Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties characteristic of both T cells and NK cells and possess a variety of unusual properties with regard to antigen recognition and function. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids. The best known subset of CD1d-dependent NKT cells expresses an invariant T cell receptor a (TCR-a) chain. These are referred to as type I or invariant NKT cells (iNKT cells). These cells, which are the main focus of the current review, are conserved between humans and mice. Detailed work in mouse models has implicated iNKT cells in many immunological processes, and related studies in humans suggest important roles in health and disease. By virtue of their ability to produce a variety of immunoregulatory cytokines and to acquire a broad spectrum of effector activities, iNKT cells may both induce or suppress immune reactions in healthy and pathologic settings. We review the role of iNKT cells in the induction of tolerance to solid organ and hematologic transplants and malignancies, as well as their importance in maintaining normal self-tolerance and involvement in autoimmune diseases.