| Allogeneic hematopoietic stem cell transplantation (alloHSCT) has revolutionized the treatment of malignant haematological disease. However, as the fewer and fewer HLA-matched donors, people have been forced to study HLA haplotype-mismatched HSCT. Compared with HLA-matched HSCT, HLA haplotype-mismatched HSCT possess favorable antileukemia effect, but there is more possibility of unsuccessful transplantation and occurrence of graft-versus-host disease (GHVD) in it. New research focus on how to decrease GHVD, how to reduce transplantation complication and how to ameliorate better life quality of recipient after transplantation under the precondition of preserving the ability of GVL in HLA haplotype-mismatched HSCT. The present methods of T cell depletion of the graft, using large dosage of immune inhibitor after transplantation and selected stem cell graft cannot fulfill this objective. New research aspect transfers to application of immune cell. Natural killer (NK) cell has the ability of antitumor and antiinfect, but the role of NK cell in HLA haplotype-mismatched bone marrow transplantation is not clear. We further research the role of donor-derived NK cell inhaplotype-mismatched BMT in C57BL/6H2bCB6F1H-2b/d transplantation model in order to provide an experiment basis of application of NK cell in clinic. With the establishment of the effectiveness of immune modulation of NK cell, more than 92% patients with malignant hematological disease will be treated by transplantation.Methods1. Study on hematopoietic reconstitution and immune tolerance induced by donor-derived NK cell of MHC haplotype-mismatched BMT in mice:The murine model of MHC haplotype-mismatched BMT was established by using (BALB/cmice as the recipient, and C57BL/6H-2b mice as the donor. 90 CB6F1H-2b/d mice were randomly divided into 9 groups after irradiation (TB Co 9.0Gy). Control groups (4 groups): the first one was simple-irradiation group, the second one was haplotype-mismatched BMT group into whom bone marrow cells of C57BL/6H-2b mice were injected after 4 hours irradiation, the third one was syngeneic BMT group into whom bone marrow cells of CB6F1H-2b/d mice were injected after 4 hours irradiation, the fourth one was haplotype-mismatched GVHD-control group into whom bone marrow cells and spleen cells of C57BL/6H-2b mice were injected after 4 hours irradiation. Experimental groups (5 groups): The CB61H-2b/d mice were conditioned with 9.0Gy in the first, second and third experimental groups and then different doses of NK cells which were 1X106/one. 5X105/one.. 2X105/one respectively were injected into them, after an interval of four hours followed by infusion of C57BL/6H-2b mice bone marrow cells. The CB6F1H-2b/d mice were conditioned with 9.0Gy in the third and the fourth groups and then different doses of NK cells which were 1 X106/one. 5X105/one respectively were injected into them, after an interval of four hoursfollowed by infusion of C57BL/6 mice bone marrow cells and spleen cells. The effect was assessed by hemotopoietic reconstruction, survival time, body weight, and histopathology in the recipients.2. Study on antileukemic activity of donor-derived NK cell in mice in vivo:CB6F mice model of EL9611 (H-2) erythroleukemia was developed by injection of EL9611 (H-2) cells in tail vein. 30 mice with erythroleukemia were randomly categorized into 5 groups (six mice in each group). Control groups (3 groups) : the first group was the one without treatment, the second one was the Ara-c-treated group which Ara-c were injected into mice at 50mg/(kg ?one) X 6d followed by infusion of EL9611(H-2) 5 days, the third one was syngeneic NK cell treated group: CB6FNK cells(1 X 10) were injected into CB6F mice after injected EL9611(H-2) cells 5 days. Experimental groups(2 groups): and 5X105 NK cells of C57BL/6 were injected into mice after injected EL9611 cells 5 days in the first and the second experimental groups. The effect was assessed by blood routine test, survival time, body weight, and histopathology in the recipients.3. Effect...
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