Effectiveness of GVHD and GVL of Donor-Derived NK Cell of MHC Haplotype-Mismatched BMT in Mice.

Abstract Objective: To study Effectiveness of GVHD and GVL of donor-derived NK cell of MHC haplotype-mismatched BMT in mice. Methods: CB6F1 H-2b/d mice model of EL9611 (H-2d) erythroleukemia was developed by injection of EL9611 (H-2d) cells in tail vein, CB6F1 H-2b/d mice as the recipient, and C57BL/6H-2b mice as the donor. 70 CB6F1 H-2b/d mice were randomly separated into 7 groups (10 mice per group). Control groups (4 groups): the first group was the one without treatment, the second one was simple-irradiation group, the third one was the Ara-c-treated group which Ara-c were injected into mice at 50mg/(kg·one)×6d followed by infusion of EL9611(H-2d) 5 days, the fourth one was haplotype-mismatched GVHD-control group which bone marrow cells and spleen cells of C57BL/6H-2b mice were injected into the mice after 4 hours irradiation. Experimental groups(2 groups): Irradiated 9Gy, mice were injected C57BL/6H-2b NK cells(1×106) and then BM cells after 4 hours in the first experimental group. After irradiation of 9Gy, mice were injected C57BL/6H-2b NK cells(1×106) and then BM cells and spleen cells after 4 hours secondly. The effect was assessed by blood routine test, survival time, body weight, and histopathology in the recipients. Results: [circ1]Life span: the survival time was (10.10±0.88) days, (9.80±0.92)days, (22.70±3.23) days and (20.10±1.73) days in the first, second, third and fifth control groups respectively, (30.10±15.95) days in the fourth control group in which the survival time of 2 mice was more than 30 days. The survival time was (39.10±18.11) days and (49.30±17.24) days in the first and second experimental groups respectively. The survival time in 4 mice of the first experimental group was more than 30 days and 7 mice of the second experimental group. The survival time of the first of experimental group was much longer than that in the first, second, third and fifth control groups (P<0.01). The survival time of the second experimental group was much longer than that in other groups (P<0.05). [circ2]Histopathology change: It was observed that the liver and spleen were enlarged and destroyed in the mice died from leukemia by leukemia cells. [circ3]It was noted that chimerism of Y chromosome appeared in mice of experimental groups of long survival time. Conclusion: The findings provide that donor-derived NK cell has the ability of antileukemia and can reduce GVHD in C57BL/6H-2b→CB6F1 H-2b/d of erythroleukemia mice (EL9611, H-2d).