Experimental study on the prevention of mouse graft-versus-host disease by delayed sequential transplantaton

Objective To study the effect of delayed sequential transplantation on acute graft-versus-host disease(aGVHD) after mouse allogeneic-bone marrow transplantation(allo-BMT).Methods C57BL/6(H-2b) mice were used as donors and BALB/c(H-2d) mice were used as recipients.The BALB/c mice,divided into four groups(n=20 each),were given 8.0 Gy total body irradiation(TBI) on day 0 and the infusion of a blend of bone marrow cells and spleen cells in four regimes respectively,i.e.: transplantation 4 h after TBI(known as classic transplantation) in group 1,transplantation from 4 h through day 3 after TBI(sequential transplantation) in group 2,transplantation on day 4 after TBI(delayed transplantation) in group 3,and transplantation from day 4 through day 7 after TBI(delayed sequential transplantation).The levels of recipient′s H-2b cells,subpopulations of T lymphocyte and NK cell were detected by flow cytometry.The survival rate,clinical manifestations of aGVHD and hematopoietic recovery in the recipient mice were observed.Results The mice in group 1 all died of aGVHD within 3 weeks after transplantation.The survival rates in groups 2 and 3 were 30% and 50% respectively on day 60.The survival rate in group 4 was 70% on day 60,which was higher than those in the other three groups(P﹤0.05).The mean value of donor-derived cell(H-2b cells) in group 4 was 98.13%±1.11% on day 60,in which the WBC count reached the normal value on day 20;the subpopulations of T lymphocyte and NK cell reached their normal values on day 30.Conclusions The delayed sequential transplantation is a simple and effective new way to prevent aGVHD after allo-BMT,improving the survival rate and bringing no bad effects onto the engraftment and the reconstitution of hematopoiesis and immunity in the recipient mice.