| Budget Amount *help |
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
1, The cardiac allograft tolerance induced by the anti-LFA-l/ICAM-1 treatment was mainly mediated by the inactivation of allogeneic classi-reactive CD8^+ T cells, whereas that induced by anti-CD/fCD48 or anti-CD8O/CD86 was mediated by Th2 deviation and/or Th1 inactivation. This suggests divergent mechanisms are responsible for allograft tolerance.
2, The cardiac allograft tolerance induced by the anti-LFA-l/ICAM-l or anti-CD8OICD86 treatment was so stable that it could not be broken by subsequent challenge with donor-type cells transduced with IL-2, IL-12, or CD8O genes.
3, Lethal GVHD after bone marrow transplantation was prevented by the administration of anti-CDBO/CD86 mAbs.
4, Short-term administration of anti-LFA-1/ICAM-l mAbs before the onset of insulitis persistently prevented the occurrence of diabetes in NOD mice.
5. Administration of anti-IL-12 mAb not only prevented the experimental autoimmune uveoretinitis (EAU) elicited by IRBP in BlO.A mice but also induced resistancy against
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the subsequent challenge with IRBP.
6. Introduction of LL-12p40 (IL-12 antagonist) gene inhibited the rejection of allogeneic myoblasts.
7. We characterized the expression and function of human and murine FasL by generating mAbs.
8, In a murine model of lethal acute GVHD, administration of anti-FasL and anti-TNFalpha mAbs led to a chimeric state of tolerance.
9, We revealed that CD8O/CD86-independent rejection of allogeneic hepatocytes is mediated by FsaIFasL system.
10, We revealed that FasL expressed on corneal endothelium critically contributes to corneal allograft survival.
11, While FasL-transfected cells underwent repid rejection by neutorphils, co-transfection of IL-b or TGF-beta inhibited the neutrophil-mediated rejection.
12, We established mAbs against mouse CD7O, OX4OL, CD3OL, and 4-1BBL and characterized the expression and function of these costimulatory molecules.
13, We established mAbs against rat CD8O, CD86, and OX4OL and characterized the expression and function of these costimulatory molecules. Less
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