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 4.5x10(6) bone marrow cells mixed with 3.0x10(7) 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 microg/ml TJU103, which was subsequently injected intraperitoneally for 7 consecutive days at daily dose of 50 microg. 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 microg/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 microg 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 (P<0.01). The median survival time (MST) was 30 days in the experimental group versus 15 days in the control group (P<0.05). 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 (P<0.01). The MST was 30 days in the experimental group versus 14 days in the control group (P<0.05).
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.