|Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥9,300,000 (Direct Cost: ¥9,300,000)
The non-MHC-encoded CD1 family provides a novel lipid antigen-presenting system that is distinct from either MHC class I or class II molecules. Whereas the group 1 CD1 (CD1a, CD1b and CD1c) were absent in rats and mice, the group 2 CD1d has been conserved through mammalian evolution including mice, rats, rabbits, sheep, and humans. CD1d molecules are expressed by a wide variety of organs, appearing strongly in the intestinal epithelium, hepatocytes, epidermal cells, and to a lesser extent in thymocytes and hematolymphoid cells. From a phylogenetic standpoint, several investigators have hypothesized that CD1d molecules have a similar functional significance in various mammalian immune systems. However, roles of CD1d in pathological basis of inflammation is not fully understand. We find, that CD1d-reactive lymphocytes are enriched in the normal liver and propagated in its inflammatory condition of liver. Detailed examination of the copper overload in an animal model and inherited human disorder (Wilson disease) revealed that that invariant CDR3 bearing NKT cells can be used as a marker of severe (fulminant) hepatitis. In the animal model, these cells directly contribute destruction of hepatocytes. On the other hand, mushroom plant workers with mild allergic inflammatory disorder of the lung experience a Th2 shift and activation of innate inflammatory cells, no evidence of increase of CD1d reactive cells and NKT cells. When the lung status become severe (hypersensitive pneurnonitis), the cells are increased. These results suggest that CD1d self reactive cells play critical roles in progression of inflammatory disorders.