Research Project
Grant-in-Aid for Scientific Research (B)
In ABO-blood group incompatible transplantation and xenotransplantation, grafted organs will be rejected because antibody (Ab)-mediated rejection is induced in responses to blood group A/B antigens, Gal α 1-3Galb1-4GlcNAc (Gal) or N-glycolylneuraminic acid (NeuGc) carbohydrates, which are widely expressed on the organ vessel epithelia. We have attempted to establish a specific immunosuppressive method targeting B cells responding to A/B, Gal and NeuGc carbohydrate antigens.In this study, we have analyzed the role of natural killer T (NKT) cells in the differentiation of B cells responding to the transplant-related carbohydrates. In the wild-type (WT) control mice, anti-A IgM/IgG Ab production occurred and was accelerated after the immunization with human red blood cells (RBCs) and α Galactosylceramide ( α GalCer) (an unique carbohydrate antigen that is presented on CD1d molecules and activates NKT cells). On the other hand, in the CD1d (ligand to the V α 14 T cell receptors used predominantly in NKT cells) knockout (KO) mice, anti-A IgM production was significantly reduced and anti-A IgG-class switching could not be observed. There was no difference in anti-allogeneic MHC Ab production between WT and CD1dKO mice, and IgG-class switching could be normally observed in both background mice. Based on these findings, it is likely that the suppressive modulation of CD1d molecule-mediated signaling between NKT cells and B cells might lead to the avoidance of Ab-mediated rejection in ABO-incompatible transplantation, whereas this strategy could not prevent Ab production from B cells responding to allogeneic MHC antigens. In order to investigate further such roles of NKT cells in the differentiation of B cells responding to the xenogeneic carbohydrate antigens, we have now established Gal/CD1d double KO mice and NeuGc/CD1d double KO mice by mating either Gal KO or NeuGc KO mice with CD1dKO mice.
All 2008 2007 2006
All Journal Article (22 results) (of which Peer Reviewed: 10 results) Presentation (50 results)
Blood 110
Pages: 4567-4575
Proceeding of the national academy of sciences of the United States of America 104
Pages: 5062-5066
American journal of transplantation 7
Pages: 2190-2194
Transplant international 20
Pages: 632-635
Blood 110(13)
Pages: 4567-75
Proc Natl Acad Sci USA 104(12)
Pages: 5062-6
Am J Transplant 7(9)
Pages: 2190-4
Transpl Int 20(7)
Pages: 632-5
Proceeding of the National Academy of sciences of the United States of America 104
Amcrican Journal of Transplantation 7
ABO不適合移植の新戦略2007 (In press)
Transplantation 82
Pages: 1712-1719
Transplant Immunology 16
Pages: 158-165
The Journal of Immumology 177
Pages: 3615-3624
American Journal of Transplantation 6
Pages: 797-805
Transplantation 82(12)
Pages: 1712-9
Transpl Immunol 16(3-4)
Pages: 158-65
J Immunol 177(6)
Pages: 3615-24
Am J Transplant 6(4)
Transplantation 82・12
Transplant immunology 16・3-4
American journal of transplantation 6・4
Pages: 797-80
