PTD-mFoxp3 fusion protein induces mixed chimerism and reduces the incidence of graft-versus-host disease
10.3760/cma.j.issn.0254-1785.2013.10.012
- VernacularTitle:PTD-mFoxp3融合蛋白诱导骨髓移植小鼠嵌合体减轻急性移植物抗宿主病
- Author:
Sanrong XU
;
Wei LI
;
Qing ZHOU
;
Bo HAN
- Publication Type:Journal Article
- Keywords:
Bone marrow transplantation;
PTD-mFoxp3 fusion protein;
Chimerism;
Graft-versus-host disease
- From:
Chinese Journal of Organ Transplantation
2013;34(10):625-629
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a stable transplantation tolerance model by combined treatment with PTD-mFoxp3 fusion protein and allogeneic bone marrow transplantation and study its application to reduce the incidence of graft-versus-host disease (GVHD).Method BALB/c mice as recipients were randomly divided into four groups,accepted medical linear accelerator ray 3.0-Gy total body irradiation (TBI) before bone marrow transplantation (BMT),and injected with donor C57BL/6 mice bone marrow cells 3 × 107withinn 4-6 h.The BALB/c mice in group A were given PTD-mFoxp3 fusion protein through tail vein intermittently (day-2,0,1,3,5,7,9,11,13),those in group B given the same dose mFoxp3 protein,those in group C given normal saline,and those in blank control group given no treatment.The symptoms of GVHD were observed after BMT.Chimerisms were determined on the week 1,2,4,8 and12 post-BMT by flow cytometry.Liver and intestinal tissues were collected for pathological examination.Recipient immune response was assessed on the week 4 and 12 by mixed lymphocyte reactions (MLR) after BMT.Results The chimerism level in group A was high [(38.16 ± 3.09) ％] in the first 12 weeks after BMT,and that in group B and group C was reduced [(20.12 ± 4.75) ％ and (15.72 ± 2.36) ％ respectively,P＜0.05].MLR revealed that shown lymphocyte donor-derived lymphocyte proliferation rate at 4th and 12th week in group A was significantly lower than in other groups (P＜0.05).Pathological examination showed infiltration of lymphocytes in the liver and intestine was milder in group A than in other groups.Conclusion PTD-mFoxp3 fusion protein combined with allogeneic bone marrow transplantation can effectively establish a stable transplantation chimeric model and reduce the incidence of GVHD.
