骨髓移植,排异反应 z-bo 2020-10-19 578

　　Bone marrow transplantation is the only effective treatment for leukemia patients, but transplant-to-host disease (GvHD) related to post-transplant rejection is a lifelong problem that patients must face. On the other hand, the anti-tumor immune response generated after transplantation and transplanted piece-by-piece leukemia (GvL) has a beneficial effect on leukemia. GvHD patients should receive CsA and FK506 treatment. These two drugs can directly inhibit the activity of calcium/calmodulin, thereby blocking the activation of T cell transcription factor NF-AT. However, clinical results showed that the symptoms of GVHD were relieved and the activity of immune cells GvL was also relieved after treatment. How to effectively inhibit GVHD while maintaining GvL activity is a very important issue.

　　Recently, the Friederikeberberg-Siebert research team of the Cancer Research Center of the University of Würzburg in Germany published a study on this issue online on the PNA. First, the author established a mouse bone marrow transplant model. After irradiation, the bone marrow cells of mice lacking NFAT were transplanted into another wild-type mouse, and the process of T cell proliferation and differentiation was observed for several days. The results showed that after removal of the NFAT transcription factor, the differentiation and spreading ability of bone marrow cells was inhibited. In addition, observations of the mouse phenotype showed that the recipient developed severe GVHD and died after transplanting bone marrow cells from wild mice, but transplanted bone marrow cells from NFAT-deficient mice. If the recipient is small. Alleviated all symptoms of rats. The study found that after the introduction of NFAT-deficient bone marrow cells, the differentiation rate of Treg in these cells was significantly improved compared with the control group. More importantly, even without NFAT, nTreg still has the ability to inhibit GVHD. It can be seen that NFAT only plays a role in the immune activation of conT cells, but has no adverse effect on Treg.

　　Then, do T cells lacking NFAT still have GvL activity? The author artificially injected fluorescently labeled IM380 tumor cells into mice. After irradiation, tumors in the control mice grew rapidly. When wild bone marrow cells were injected through bone marrow transplantation, tumors grew significantly. However, mice develop complications of GvHD and die quickly. Interestingly, injection of bone marrow cells lacking NFAT not only successfully eliminated tumors in mice, but also significantly reduced the complications of GvHD. All in all, through a large number of in vivo experiments, the authors proved that the lack of NFAT can reduce the adverse effects of bone marrow transplantation, while retaining the benefits of neonatal immune response. FAT can also be used as a possible target for immunotherapy after leukemia bone marrow transplantation.