| Organ transplantation is the hot issue of the medical research in the 21st century, and it has made great progress in the recent years. How to establish the donor specific transplantation tolerance is the key step in the organ transplantation. The donor specific transplantation tolerance is used to avoid the problems which are caused by using immunosuppressant for life long. In the research of the mechanism of tolerance, researchers discovered that regulatory T cell is a kind of cell subsets which has the function to inhibit the immune response and it also plays an important role in maintaining the balance between immunity and tolerance. A great number of proliferative regulatory T cells can induce tolerance. Nowadays, Notch signaling pathway is the hot point in the field of auxology, immunology and oncology. It is important for the systemoid development, the auxano-differentiation of the immunologic cell and the tumorigenesis. However, there is no literatures published about the Notch signaling pathway in inducing transplantation tolerance in the world.Based on preliminary work, we did this research to further study the mechanism of hematopoietic stem cell transplantation in inducing tolerance. We studied the effect of Notch signaling pathway in syngeneic hematopoietic stem/progenitor cell transplantation in inducing tolerance by detect the expression of Jagged2 which is the specificity ligand in the Notch signaling pathway.Aim: We establish cervical heterotopic cardiac transplantation model in mice, study the effect of Notch signaling pathway in syngeneic hematopoietic stem/progenitor cell transplantatio in inducing tolerance, and explore a new safe way to induce specific transplantation tolerance.Method: The mice were randomly divided into 4 groups. Cervical heterotopic cardiac transplantation model in mice was established in all groups. Mice in group D were untreated while those in group A and B were treated with hematopoietic progenitor cell transplantation , group C were treat with hematopoietic stem cell transplantation. We use Notch signaling specific block agent DAPT in Group B. Expression of Notch ligand Jagged2 in the hematopoietic stem/progenitor cells was detected by flow cytometry. After hematopoietic stem/progenitor cell transplantation, perform cervical heterotopic cardiac transplantation model, and recorded the cardiac allograft survival time and constructed Kaplan-Meier survival curve. Compare the difference of the survival time of the cardiac allograft among all groups. Make tissue slices for the cardiac allograft and stain the slices with HE and Masson. Compare the pathological change among all groups. Treg in peripheral blood was analyzed by FCM. The specification of induced tolerance was detected by mixed lymphocyte reaction.Result:1. Jagged2~+ cell is(59.6±3. 5)% and (60.2±4.1)% in group A and group B respectively, both are HPCs, and neither difference was statistically significant, p>0.05. But in group C, which is HSC, the Jagged2+ cell is (32.8±3.2)%. Compared with group A and group B, there were significant differences, p>0.05.2. Kaplan-Meier survival curve showed that there has significant difference of the survival time of the cardiac allograft among all groups. 62.5% of the grafts in group A showed long-term survival (>100 days), while none in other groups.3. The pathological change in group D was acute rejection. There were little pathological change in group A and C within a week while only tiny changes in group B.4.The percentage of Treg cells in peripheral blood of recipients after transplantation peaks at 4th week then declines according to FCM. It is significantly higher in group A than those in group C at every observation time spot. The survival time of group B and is too short to do statistical analysis.5. MLR showed that mice in group A and C had lower responsibility to lymphocyte from donor while higher to that from third-party.Conclusion: Notch signaling pathway can precipitate the generation of the Treg to induce the immunotolerance by the interaction of the receptor and ligand. This way can prolong the survival time of the cardiac allograft and play an important role in the procession of tolerance induced by syngeneic stem/progenitor cell transplantation. It has donor specificity in transplant immunotolerance by this method.
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