[Role of TJU103 in prevention of graft-versus-host disease after allogeneic stem cell transplantation in mice].

Objective To explore the role of TJU103 in preventing graft-versus-host disease (GVHD) after allogeneic stem cell transplantation in mice. Methods BALB/c mouse splenic lymphocytes were collected and treated by mitomycin as the activating cells and the C57BL/6 mouse splenic lymphocytes as the reacting cells. In the experimental groups, the effect of TJU103 on the proliferative response of T cells was observed. BALB/c(H-2d) and CB6F1(H-2d/b) mice were used as the MHC-full-mismatched recipients and MHC-haplo-identical recipients, respectively, and pretreated by total body irradiation at 9.0 Gy before transplantation. For the recipients of the irradiation group, 0.3 ml D-Hank's solution was injected through the tail vein without cell transplantation, the recipients of the control group received injection of 4.5×106 bone marrow cells mixed with 3.0×107 spleen cells from C57BL/6 mice through the tail vein, and those in the experimental group received cell transplantation in the same manner with also injection via the tail vein of 25 μg/ml TJU103, which was subsequently injected intraperitoneally for 7 consecutive days at daily dose of 50 μg. The hematopoietic recovery, engraftment and GVHD of the recipients were observed. Results TJU103 resulted in a dose-dependent inhibition of T cell proliferation in mixed lymphocyte reaction (MLR), and nearly 83% inhibition of the proliferative response was observed with the addition of 25 μg/ml of TJU103. Without any treatment, the occurrence of GVHD and death rate in the control group was both 10/10. Daily injection of TJU103 at 50 μg for the initial post-transplantation week protected the mice from GVHD. In the MHC-full-mismatched model, the incidence of GVHD and survival rate on day 30 of the experiment group was 2/10 and 8/10, showing significant difference from those in the control group (P0.01). The median survival time (MST) was 30 days in the experimental group versus 15 days in the control group (P0.05). In the MHC-haplo-identical model, the incidence of GVHD and the survival rate on day 30 of the experimental group was 1/10 and 9/10, which were significantly different from the control group (P0.01). The MST was 30 days in the experimental group versus 14 days in the control group (P0.05). Conclusion TJU103 is capable of markedly inhibiting T cell proliferative response in vitro and can decrease GVHD incidence after allogeneic stem cell transplantation in mice.