Diversity of CD1d-restricted natural killer T cells

The present study deals with natural killer (NK) T cells restricted to the antigen presenting molecule CD1d. NKT cells have been suggested to play a role in many diverse immunological situations such as clearance of different pathogens, protection against certain tumors, regulation of autoimmune reactions and as a link between innate and adaptive immune responses. NKT cells are in many respects unique. They recognize lipid and glycolipid antigens associated with CD1d, rather than peptides. Furthermore, the frequency of CD1d-autoreactive NKT cells is high which suggests that self-antigens are the natural ligands for at least some NKT cells. Also, NKT cells are potent cytokine producers upon activation and they may play a role in the development of Th1 and Th2 immune responses. We have been able to show that the NKT cell population is very heterogeneous both regarding their phenotype and function. By generating a T cell receptor (TCR) transgenic mouse, we were able to show that NKT cells with a diverse TCR had the expected NKT cell phenotype and were potent cytokine producers. We demonstrate that the activity of potentially CD1d-autoreactive NKT cell subsets can be regulated with the help of inhibitory Ly49 receptor and that expression of Ly49 receptors correlate with a certain T cell receptor repertoire and cytokine profile. With the identification of functionally different NKT cell subsets regarding their cytokine profile, we will increase our understanding on how NKT cells are able to play such diverse immunological roles.