| Project/Area Number |
13671669
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
YOSHIMURA Rikio Osaka City University, Graduate School of medicine, assistant, 大学院・医学研究科, 助手 (50285293)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Tatsuya Osaka City University, Graduate School of medicine, associate professor, 大学院・医学研究科, 助教授 (40183511)
山本 啓介 大阪市立大学, 大学院・医学研究科, 教授 (70137230)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | Natural killer T cells / CD3 / CD56 / umbilical cord blood |
|---|
| Research Abstract |
Natural killer T cells in this model were shown to induce accelerated rejection. This effect could be specific for the NK cells or would be the results of a cooperation between the NK cells (secretion of cytokines) and T cells (as allocytotoxic effectors). From our study, not only T cells but also NK cells may play a role in organ transplantation rejection. NK-T cells may induce immune tolerance in organ transplantation. However, this mechanism using specific immune therapy for the induction of tolerance or to increase anti-cancer cytotoxic activity needs further study. These data confirm the inhibitory role of host NK cells in stem cell allogeneic engraftment. We have demonstrated the beneficial effect of anti-NK treatment. Treatment with anti-asialo-GM1 provides a means for improving the immunologjc conditioning of the recipient and showed no harmful effects. NK-cell activity was actually restored a few week after a brief inhibition, which may contribute strongly to maintaining a stable chimerism. Our data are comparable to those obtained with a lethally irradiated model reconstituted by more important semi-allogeneic FLCT mixed with a mature T-cell donor-which became activated and released cytokines. CD3^+ /CD56^+ cells, low in freshly isolated UCB, proliferated significantly in bulk MLC and represented a majority of the responders after single cell cloning. These cells expressed the CD8^+ phenotype and a few N-specific cells proliferated and exhibited an MHC-restricted killing activity. Cytokine production on the UCB clones was lower than in the PB clones, despite their stronger killing activity. The CD3^+ CD8^+ T cells, expressing, the CD56^+ marker, could be the major cells responsible for title induction of GVHD. They should be proven in HLA-mismatched UCB transplantation.
|
