Influence of mycophenolate mofetil (MMF) upon thematuration and allo-stimulatory activity of cultured progenitors of dendritic cells and the effectson the tolerance induction in allograft recipients  

作　　者：CONGHUIHAN YUXINWANG QINGLIANG MINGZHANG YINGWANG MINGYIN ZHILIANMING KELIZHENG 

机构地区：[1]不详 [2]DepartmentofUrology,AffiliatedXuzhouHospitalofSoutheastUniversity,Xuzhou,P.R.China [3]DepartmentofOrgan-TransplantationandLaboratoryofKidney-Transplantaion,FifthAffiliatedHospitalofSunYet-SenUniversity,Zhuhai,P.R.China [4]CenterofOrgan-Transplantation,AffiliatedChangzhengHospitaltheSecondMilitaryMedicalUniversityofPLA,Shanghai,P.R.China [5]MedicinalCollege,theSecondMilitaryMedicalUniversityofPLA,Shanghai,P.R.China

出　　处：《Journal of Microbiology and Immunology》2005年第1期73-80,共8页中华微生物学和免疫学（英文版）

摘　　要：To investigate the influence of mycophenolate mofetil (MMF) upon the maturation and the allo-stimulatory activity of cultured progenitors of dendritic cells (DCp), and to evaluate the effects of the pre-treated dentritic cells of recipients with MMF on the tolerance induction as well as its possible mechanism, GM-CSF and MMF were added to the in vitro cultured progenitor cells, and the immuno-phenotypical analysis was performed by means of flow cytometry. The secretion of IL-12 was detected by ELISA and the stimulatory activities of DCp on allogeneic T cells were observed by mixed lymphocyte reaction. Twenty-four C57BL/6 mice were divided into 3 groups (each with 8 mice), in which group A of mice accepted allografts of heart from BALB/c mice, group B of mice had received untreated DCp from donors of BALB/c mice 7 days before transplantation, and C57BL/6 mice in group C were treated by injection with MMF-treated allografts of heart from BALB/c mice 7 days before transplantation. The survival times of allografts and the changes of the cytokine levels in sera of the recipient mice were observed after transplantation. The experimental results showed that MMF could significantly inhibit the expressions of the co-stimulatory molecules CD80 and CD86 on DCs and the secretion of IL-12 and the allo-stimulatory activities of DCs were also markedly inhibited. The survival times of allografts in group B of mice were longer than those in group A, while the group C showed the longest survival times of allografts, with a marked reduction in the production of the Th1 type cytokines. It is evident that MMF has a suppressive effect on the maturation and allo-stimulatory activities of the cultured dendritic cell progenitors, thus leading to a donor specific tolerance in heart-transplanted recipients.To investigate the influence of mycophenolate mofetil (MMF) upon the maturation and the allo-stimulatory activity of cultured progenitors of dendritic cells (DCp), and to evaluate the effects of the pre-treated dentritic cells of recipients with MMF on the tolerance induction as well as its possible mechanism, GM-CSF and MMF were added to the in vitro cultured progenitor cells, and the immuno-phenotypical analysis was performed by means of flow cytometry. The secretion of IL-12 was detected by ELISA and the stimulatory activities of DCp on allogeneic T cells were observed by mixed lymphocyte reaction. Twenty-four C57BL/6 mice were divided into 3 groups (each with 8 mice), in which group A of mice accepted allografts of heart from BALB/c mice, group B of mice had received untreated DCp from donors of BALB/c mice 7 days before transplantation, and C57BL/6 mice in group C were treated by injection with MMF-treated allografts of heart from BALB/c mice 7 days before transplantation. The survival times of allografts and the changes of the cytokine levels in sera of the recipient mice were observed after transplantation. The experimental results showed that MMF could significantly inhibit the expressions of the co-stimulatory molecules CD80 and CD86 on DCs and the secretion of IL-12 and the allo-stimulatory activities of DCs were also markedly inhibited. The survival times of allografts in group B of mice were longer than those in group A, while the group C showed the longest survival times of allografts, with a marked reduction in the production of the Th1 type cytokines. It is evident that MMF has a suppressive effect on the maturation and allo-stimulatory activities of the cultured dendritic cell progenitors, thus leading to a donor specific tolerance in heart-transplanted recipients.

关 键 词：Dendritic cells Mycophenolate mofetil Immune tolerance 

分 类 号：R654.2[医药卫生—外科学] R392.4[医药卫生—临床医学]