首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection.
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Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection.

机译:治疗性树突状细胞和调节性T细胞的生成,可防止同种异体心脏移植排斥。

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摘要

Tolerogenic dendritic cells (Tol-DCs) and regulatory T cells (Treg) are key factors in the induction and maintenance of transplantation tolerance. We previously demonstrated that ex vivo-isolated Tol-DCs promote Treg generation, and vice versa, in an in vitro co-culture system. Here we demonstrate the occurrence of such an immune regulatory feedback loop in vivo. Tol-DC generated in vitro by treatment with LF 15-0195 exhibited features of immature DC and express low levels of MHC class II, CD86 and CD40. These Tol-DCs were capable of augmenting CD4(+)CD25(+)CTLA4(+) and FoxP3(+) Treg cell numbers and activity in cardiac allograft recipients. On the other hand, Tol-DCs possessed an ability to generate Treg cells in vitro. The adoptive transfer of these in vitro-generated Treg cells resulted in an increase of Tol-DC in vivo, suggesting that an immune regulatory feedback loop, between Tol-DC and Treg, exists in vivo. Furthermore, the administration of in vitro-generated Tol-DCs or Treg cells prevented rejection of allografts. Co-administration of Tol-DC and Treg synergized efficacy of promoting allograft survival heart transplantation. The present study highlights the therapeutic potential of preventing allograft rejection using in vitro-generated Tol-DCs and Treg.
机译:致耐受性树突状细胞(Tol-DCs)和调节性T细胞(Treg)是诱导和维持移植耐受性的关键因素。我们先前证明,在体外共培养系统中,离体分离的Tol-DCs促进Treg生成,反之亦然。在这里,我们证明了这种免疫调节反馈回路在体内的发生。通过用LF 15-0195处理体外产生的Tol-DC表现出不成熟DC的特征,并表达低水平的MHC II类,CD86和CD40。这些Tol-DCs能够增强心脏同种异体移植受者的CD4(+)CD25(+)CTLA4(+)和FoxP3(+)Treg细胞数量和活性。另一方面,Tol-DC具有在体外产生Treg细胞的能力。这些体外产生的Treg细胞的过继转移导致体内Tol-DC的增加,这表明Tol-DC和Treg之间存在免疫调节反馈回路。此外,给予体外产生的Tol-DC或Treg细胞可防止同种异体移植排斥。 Tol-DC和Treg的共同给药具有促进同种异体移植存活心脏移植的协同功效。本研究强调了使用体外产生的Tol-DC和Treg预防同种异体移植排斥的治疗潜力。

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