[Effect of delayed sequential bone marrow transplantation on acute graft-versus-host disease in major H-2 incompatible mouse transplantation].

OBJECTIVE: To study the effect of delayed sequential bone marrow transplantation on acute graft-versus-host disease (aGVHD) in major H-2 incompatible mouse transplantation. METHODS: C57BL/6 (H-2b) mice were used as donors and BALB/c (H-2d) mice as recipients. BALB/c mice were given 8.0 Gys total body irradiation (TBI) on day 0 and infused with a blend of bone marrow cells and spleen cells in different time. Transplantation was carried out as follows: group I TBI on day 0 and transplantation at 4 h after TBI; groups of II TBI on day 0 and transplantation at 4 h, d1, d2, d3 after TBI; groups III TBI on day 0 and transplantation at day 4 after TBI; groups IV TBI on day 0 and transplantation at day 4 through day 7 after TBI. Recipient's spleen H-2b cells were detected by flow cytometry and the level of serum cytokines (IL-2, IL4, IL-6, IL-10 and IFN-gamma) by ELISA. The survival, aGVHD and hematopoietic recovery were observed. RESULTS: aGVHD occurred in group I and the mice all died within 3 weeks after transplantation. The 60 day survival rates of groups of II and III were 30% and 50% respectively. The degree of aGVHD in group III was modest and the survival rate was higher than that in other groups (P <0.05). The peak time of IL-2, IFN-gamma, IL-4 and IL-10 in groups III and IV were later than that in group I. The levels of IL-4 and IL-10 in groups III and IV were higher than that in group I and for the levels of IL-2 and IFN-gamma were on the contrary (P < 0.05). The level of IL-6 in all groups peaked on day 5 to day 10 after TBI and was higher in group I than in others (P <0.05). In group IV the mean value of donor H-2b cells was (98.1 +/- 1.1)% on day 60 and WBC counts recovered normal on day 20. CONCLUSIONS: Delayed sequential transplantation can reduce the morbidity of aGVHD ,improve the survival rate and not affect the engraftment and reconstitution of hematopoiesis in mouse allo-BMT. The mechanism of aGVHD prevention may be related to the reducing of type 1 cytokines of T lymphocyte and the increasing of type 2 cytokines.