| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Allogeneic bone marrow transplantation (BMT) is the only curative treatment for hematopoietic malignancies such as leukemia, lymphoma, and myelodysplastic syndromes, and severe aplastic anemia. However, graft-versus-host disease (GVHD) often develops after allogeneic bone marrow transplantation and it is one of the major complications since severe GVHD leads to a fatal outcome. Therefore, the control of GVHD is the most important matter in order to increase the success rate of allogeneic BMT.GVHD is caused by the failure of induction of immunological tolerance. T cells in the donor marrow respond to the histocompatibility antigens of the host. Thereafter, various cytokines can be produced, resulting in the proliferation and activation of alloreactive T cells. Adhesion molcules are required to proceed the antigen recognition by T cell receptor and cytokines are essential for further proliferation and activation of T cells. Thus, we analyzed the correlation between GVHD and adhesion molecules or cytokines and we determined the important role of these factors in immunological tolerance. Costimulatory molecules (e.g., CD28 and CTLA4) and adhesion molecules (e.g., ICAM1 and VLA4) playd a pivotal role in the augmentation of GVHD.Furthermore, it became obvious that the balance between inflammatory cytokines such as IL-1, IL-6, and TNFalpha and immunosuppressive cytokines such as IL-4, IL-10 and IL-13 was important to inhibit GVHD,leading to the induction and maintenance of immunological tolerance. These results suggest that the effective blocking of these factors is promising to increase the success rate of allogeneic BMT.
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