Induction of tolerance in MHC haploidentical bone marrow transplantation in mice by combination of Tju103 and CTLA4-Ig / 中华器官移植杂志

ABSTRACT

Objective To observe the effect of combination of Tju103 and CTLA4-Ig on engraftment, graft versus host disease (GVHD), graft versus leukemia (GVL) and anti-infection post major histocompatibility complex (MHC) haploidentical bone marrow transplantation in mice in order to seek an effective access to transplantation with less GVHD and more potential GVL and anti-infection.Methods In the presence of the recipient's antigen (normal CB6F1, H-2 bd) as a stimulus for induction of specific immune tolerance, T cells from the MHC haploidentical donors (C57BL/6, H-2 b) were first in vitro cultured with Tju103 and CTLA4-Ig, then were transfused with the donors' bone marrow cells into the preconditioned recipients. At last, the effect of combination of Tju103 and CTLA4-Ig on hematopoietic rebuilding, GVHD, GVL and anti-infection was observed in compared with CsA, Tju103 and CTLA4-Ig as controls.Results The only irradiated group (group A) All the mice (10 mice) died of failure of hematopoiesis within 11 days post irradiation, of which most (8 mice) died within 4～7 days post transplantation. The CTX-treated leukemia group (group B) All the mice (10 mice) died of leukemia within 16～23 days post leukemia cells infusion (11～18 days post BMT). CTX treatment prolonged the survival time. The only transplanted group (group C) The mice began to die from day 16 post transplantation, and all (10 mice) died of GVHD within 3 weeks. The CsA prophylaxis group (group D) 4 mice died within 8～22 days after transplantation, of which one died of leukemia, two died of infection and one died of GVHD, and the remaining 6 survived over 30 days post transplantation. The Tju103 treated group (group E) 4 mice died within 9～26 days post transplantation, of which one died of leukemia, one died of infection and two died of GVHD, and the remaining 6 mice survived over 30 days post transplantation. The CTLA4-Ig treated group (group F) 3 mice died within 14～23 days after transplantation, of which one died of infection and two died of GVHD, and the remaining 7 survived over 30 days post transplantation. The Tju103/CTLA4-Ig treated group (group G) one died of GVHD on day 19 after transplantation, and the remaining 9 mice survived over 30 days post transplantation. Conclusions CsA, Tju103 or CTLA4-Ig alone could prolong survival time and reduce incidence and degree of GVHD severity. But CTLA4-Ig could spare much ability of GVL and anti-infection while Tju103, just like CsA, couldn't. Combination of both was the most favorable way for transplantation with the most remarkable efficiency on prolongation of survival time and reduction of GVHD.