Autoimmune diseases are caused by pathogenic antibody and/or T-cell responses that are left unchecked by regulatory immune mechanisms. Recent studies in immunology have focused on subsets of regulatory T cells (T(regs)) that can suppress autoimmune responses. Invariant natural killer T (iNKT) cells are a subset of T(regs) that recognize glycolipid antigens in the context of CD1d proteins. iNKT cells play a suppressive role in several autoimmune diseases and, therefore, are attractive targets for development of immunotherapies for these diseases. While preclinical studies with reagents, such as the sea sponge-derived iNKT-cell antigen alpha-galactosylceramide, have been promising, there are substantial concerns about treating humans with autoimmunity, or at risk of developing autoimmunity, with these reagents.