Project/Area Number |
09670798
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | Mie University |
Principal Investigator |
AZUMA Eiichi Mie University, Hospital, Associate Professor, 医学部附属病院, 助教授 (50211008)
|
Co-Investigator(Kenkyū-buntansha) |
SAKURAI Minoru Mie University, School of Medicine, Professor, 医学部, 教授 (40024707)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | cord blood transplantation / dendritic cell / T cell / NK cell / Dendritic cell / 臍帯血幹細胞移植 / T cell / NK cell / cord blood transplant |
Research Abstract |
In cord blood transplantation, low incidence of graft-vs.-host disease (GVHD) has been observed. However, it may lead to less graft-vs.-leukemia (GVL) effect. It, is not known that low incidence of GVHD is associated with more leukemia relapse. There are two major effectors to induce GVHD.The first one is T cells. We have previously reported that cord blood T cells can give rise to allo-specific cytotoxic T lymphocyte (CTL) just like adult T cells. The second one is blood natural killer (NK) cells. Although it has been reported that cord blood NK cells have lower NK activity than adult NK cells, we have found that cord blood NK cells can induce apoptosis and necrosis of target leukemia cells K562.Interleukin2-acitivated NK cells augmented apoptosis of K562 target. These results suggest that cord blood NK cells can be utilized to induce GVHD and to kill leukemia cells. Dendritic cells as most efficient antigen-presenting cells have a role in inducing GVHD.We have isolated dendritic cells from cord blood or cytokine-induced dendritic cells from CD34+ cells in cord blood. Corticosteroid inhibited the differentiation of dendritic cells, however antigen-presenting capacity was not inhibited. In cord blood transplantation, platelet recovery is significantly delayed. Thus, thrombopoietin (TPO) may be need. We have found that dendritic cells express TPO receptor c-Mpl and its messenger RNA by flow cytometry, immunohistochemistry, and RNase protection assay. However, TPO do not enhance the antigen-presenting capacity of dendritic cells. These results suggest that TPO may be administered following cord blood transplantation.
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