Type II natural killer T cells: a new target for immunomodulation?

Natural killer (NK) T lymphocytes are potent immunoregulatory cells that can regulate diverse immune responses. NK T cells display a low degree of inherent autoreactivity and are activated by endogenous or pathogen-specific glycolipids presented on the cluster of differentiation (CD)1d molecule. Recent studies have focused attention to type II NK T cells, which, in contrast to type I NK T cells, display a diverse T-cell receptor repertoire. Type II NK T cells in mice and humans demonstrate a unique regulatory role in autoimmunity, tumor immunity and infections. Immunotherapy targeting type II NK T cells in experimental models prevents autoimmune disease and protects mice from experimental hepatitis. Current efforts aim to reveal the underlying regulatory mechanisms of type II NK T cells in mice and humans and to identify the parameters that guide their activation, working toward the development of selective immunotherapies targeting type II NK T cells in autoimmunity and other immune-mediated diseases.