Negative selection of Th1-skewed NKT cells by the thymic epithelial CD1d (82.8)

Abstract NKT cells are a specialized subset of T cells mainly utilizing invariant Vα14-Jα18 chain for their T cell receptor. Unlike conventional T cells which are dependent on MHC class I or II, NKT cells are dependent on a MHC class I-like molecule, CD1d, for their development. Unlike MHC class I and II molecules, which support both of the positive and negative selection of conventional T cells, it was not clear whether CD1d also participate in negative selection of NKT cells. By comparing the NKT cell population and their characteristics in CD1d-deficient Vα14 transgenic mouse and CD1d-deficient Vα14/Eα-CD1d double transgenic mouse, we found that a subset of NKT cells with the phenotype of NK1.1+, CD44high, CD69high and showing Th1-skewed cytokine production was subjected to the negative selection by the CD1d expressed in thymic epithelial tissue. These results suggest that CD1d is critical not only for the positive selection of NKT cells, but also for the negative selection of NKT cells which have potentially harmful excessive self reactivity.