Molecular mechanisms of NKT cells' differentiation and functions

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It is known that NKT cells are a critical and specific cells regulating the immune system which produce both IFN-γ and IL-4 by the injection of KRN7000 (α-Galactosylceramide). In this study, we have discovered that the antigen receptors on NKT cells rapidly down-regulate and NKT cells itself disappear in sight when KRN7000 bind to the receptors (Harada, et al.2004 Int Immunol). This result is significant in understanding the mechanism of NKT cells after the activation by KRN7000.An important part was to identify genes responsible for NKT differentiation in a process known as microarray and subtraction. As a result, we have cloned a new receptor, KLRE-1,which is strongly expressed in NK and NKT cells rather than any other lymphocytes (Koike, et al.2004 JEM). By generating and analyzing KLRE-1 knockout mouse, we have found that this molecule is essential in rejection of allogenic cells (Shimizu, et al.2004 Blood).It is also important to identify the role of NKT cells in human immunity. We have examined the relationship between other immuno-regulatory cells including dendritic cells and NKT cells. In this study, we found that a single stimulation of NKT cells give rise to the reaction of Th1-type response, while the multiple stimulation suppress the immunity. We have been trying to identifying the molecule which is responsible for this reaction.