Dendritic cell therapies in transplantation revisited: deletion of recipient DCs deters the effect of therapeutic DCs.
Dendritic cell therapies in transplantation revisited: deletion of recipient DCs deters the effect of therapeutic DCs.
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DOI：
10.1111/j.1600-6143.2012.04060.x
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Morelli AE
中科院分区：
文献类型：
--
作者：
Wang Z;Divito SJ;Shufesky WJ;Sumpter T;Wang H;Tkacheva OA;Wang W;Liu C;Larregina AT;Morelli AE
移植的一个关键目标是实现供体特异性耐受，最大限度地减少免疫抑制剂的使用。树突状细胞（Dendritic cells，DCs）是一种抗原提呈细胞（antigen presenting cells，APC），具有促进免疫或耐受的功能。DC的免疫调节特性已被用于产生致耐受性/免疫抑制性（IS）DC，当全身转移时，其延长同种异体移植物在鼠模型中的存活。令人惊讶的是，移植中基于（供体或供体来源的）ISDC的治疗的体内机制仍然未知，因为先前的研究研究了它们在体外或移植后离体的作用。由于一旦注射，ISDC是短暂的，并将Ag转移到受体APC，我们通过在心脏移植的小鼠模型中ISDC治疗时耗尽受体DC来评估受体DC的作用。结果表明，与公认的范例相反，全身施用的ISDC降低同种异体反应并延长同种异体移植物存活，不是通过自身，而是通过受体的常规DC（cDC）。这些发现对目前使用的ISDC疗法的优势提出了质疑，因为注射的ISDC的免疫调节特性似乎在体内不具有功能相关性，并且cDC的静止/促耐受性状态可能在需要移植的终末期疾病患者中受到损害。
A critical goal in transplantation is the achievement of donor-specific tolerance, minimizing the use of immunosuppressants. Dendritic cells (DCs) are antigen (Ag) presenting cells (APCs) with capability to promote immunity or tolerance. The immune-regulatory properties of DCs have been exploited for generation of tolerogenic/immunosuppressive (IS) DCs that, when transfer systemically, prolong allograft survival in murine models. Surprisingly, the in vivo mechanisms of therapies based on (donor- or recipient-derived) ISDCs in transplantation remain unknown, given that previous studies investigated their effects in vitro, or ex vivo after transplantation. Since once injected, ISDCs are short-lived and transfer Ag to recipient APCs, we assessed the role of recipient DCs by depleting them at the time of ISDC-therapy in a mouse model of cardiac transplantation. The results indicate that, contrary to the accepted paradigm, systemically administered ISDCs reduce the allo-response and prolong allograft survival, not by themselves, but through conventional DCs (cDCs) of the recipient. These findings raise doubts on the advantages of the currently used ISDC-therapies, since the immune-regulatory properties of the injected ISDC do not seem to be functionally relevant in vivo, and the quiescent/pro-tolerogenic status of cDCs may be compromised in patients with end-stage diseases that require transplantation.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
20.3
作者：
Laffont, Sophie;Seillet, Cyril;Guery, Jean-Charles
通讯作者：
Guery, Jean-Charles
DOI：
10.1111/j.1600-6143.2009.02578.x
发表时间：
2009-04
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Brennan TV;Jaigirdar A;Hoang V;Hayden T;Liu FC;Zaid H;Chang CK;Bucy RP;Tang Q;Kang SM
通讯作者：
Kang SM