Role of type IINKT cells in the suppression of graft-versus-host disease

Natural killer T (NKT) cells, a distinct subset of T cells that recognize glycolipids on CD1d molecules, express both TCR and NK receptors and are critical in regulating various immune responses by modulating the Th1/Th2 balance. Upon activation, NKT cells produce large amounts of IL-4 and IFN-gamma, resulting in the enhancement or inhibition of immune responses. Recent studies have shown that NKT cells are heterogeneous in terms of the expression of a specific V alpha chain of TCR (V alpha 14-J alpha 18 in mice and V alpha 24-J alpha Q in humans) and reactivity against the glycolipid alpha-galactosylceramide (alpha-GalCer). Accordingly, NKT cells are classified into type I (invariant) and type 11 (non-invariant) cells in mice and humans. Although the functional roles of type I NKT cells are well characterized in various immune diseases, little is known regarding the function of type II NKT cells. Recent study has demonstrated that type II NKT cells in donor bone marrow play protective roles in graft-versus-host disease (GVHD), in which the complicated immunologic processes are involved. In this review, we discuss the pathogenesis of GVHD and the distinct functions of type 11 NKT cells in the development of GVHD.