Tolerance induction by exosomes from immature dendritic cells and rapamycin in a mouse cardiac allograft model.
Tolerance induction by exosomes from immature dendritic cells and rapamycin in a mouse cardiac allograft model.
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DOI：
10.1371/journal.pone.0044045
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dou KF
中科院分区：
文献类型：
--
作者：
Li X;Li JJ;Yang JY;Wang DS;Zhao W;Song WJ;Li WM;Wang JF;Han W;Zhang ZC;Yu Y;Cao DY;Dou KF
树突状细胞(DC)释放具有生物活性的外体，在免疫调节中发挥重要作用。供体未成熟树突状细胞(Imdex)来源的外切体能低水平表达I类主要组织相容性复合体(MHC)和共刺激分子，通过抑制T细胞活化延长移植物存活时间。然而，当单独使用Imdex时，这种作用是有限的，不会诱导免疫耐受。因此，我们测试了供体Imdex和小剂量雷帕霉素联合治疗在小鼠心脏移植模型中诱导耐受的效果。从供体小鼠(C57BL/6)骨髓来源的未成熟DC的培养上清液中获得Imdex，并在移植前和移植后分别向受体小鼠(BALB/c)注射亚适量雷帕霉素。利用小鼠心脏移植模型，分析了该治疗方法在体外和体内诱导免疫耐受的能力。供者Imdex表达中等水平的MHC II类分子和低水平的MHC I类分子和共刺激分子，但Imdex和亚治疗剂量的雷帕霉素均不能单独诱导同种异体心脏移植耐受。然而，Imdex和雷帕霉素联合治疗导致了供者特异性的同种异体心脏移植耐受。这一效应伴随着受者抗供体抗原细胞反应的降低和脾CD4+CD25+T细胞百分比的增加。此外，这种供者特异性耐受可以通过注射耐受受者的脾细胞而不是血清进一步传递给幼稚的同种异体移植受者。供者Imdex联合免疫抑制治疗可延长同种异体心脏移植物存活时间，诱导供者特异性移植耐受。
Dendritic cells (DCs) release bioactive exosomes that play an important role in immune regulation. Because they express low levels of class I major histocompatibility complex (MHC) and co-stimulatory molecules, exosomes derived from donor immature DCs (imDex) prolong allograft survival by inhibiting T-cell activation. However, this effect is limited and does not induce immunological tolerance when imDex are administered alone. Thus, we tested the effect of combined treatment with donor imDex and low-dose rapamycin on inducing tolerance in a mouse cardiac transplantation model. ImDex were obtained from the culture supernatant of immature DCs derived from donor mouse (C57BL/6) bone marrow and were injected with suboptimal doses of rapamycin into recipient mouse (BALB/c) before and after transplantation. The capacity of this treatment to induce immune tolerance was analyzed in vitro and in vivo using the mouse cardiac transplantation model. Donor imDex expressed moderate levels of MHC class II and low levels of MHC class I and co-stimulatory molecules, but neither imDex nor subtherapeutic rapamycin dose alone induced cardiac allograft tolerance. Combined treatment with imDex and rapamycin, however, led to donor specific cardiac allograft tolerance. This effect was accompanied by decreased anti-donor antigen cellular response and an increased percentage of spleen CD4+CD25+ T cells in recipients. Furthermore, this donor specific tolerance could be further transferred to naïve allograft recipients through injection of splenocytes, but not serum, from tolerant recipients. Combined with immunosuppressive treatment, donor imDex can prolong cardiac allograft survival and induce donor specific allograft tolerance.
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1型糖尿病患者的雷帕霉素单药治疗可修饰CD4+CD25+FOXP3+调节性T细胞。
影响因子：
7.7
作者：
Monti, Paolo;Scirpoli, Miriam;Maffi, Paola;Piemonti, Lorenzo;Secchi, Antonio;Bonifacio, Ezio;Roncarolo, Maria-Grazia;Battaglia, Manuela
通讯作者：
Battaglia, Manuela
影响因子：
4.4
作者：
Sallusto, Federica;Lanzavecchia, Antonio
通讯作者：
Lanzavecchia, Antonio
影响因子：
7.4
作者：
Morse MA;Garst J;Osada T;Khan S;Hobeika A;Clay TM;Valente N;Shreeniwas R;Sutton MA;Delcayre A;Hsu DH;Le Pecq JB;Lyerly HK
通讯作者：
Lyerly HK
影响因子：
20.3
作者：
Hackstein, H;Taner, T;Thomson, AW
通讯作者：
Thomson, AW
影响因子：
2.2
作者：
Lamparski, HG;Metha-Damani, A;Le Pecq, JB
通讯作者：
Le Pecq, JB