Preemptive donor apoptotic cell infusions induce IFN-γ-producing myeloid-derived suppressor cells for cardiac allograft protection.
Preemptive donor apoptotic cell infusions induce IFN-γ-producing myeloid-derived suppressor cells for cardiac allograft protection.
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DOI：
10.4049/jimmunol.1302771
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发表时间：
2014-06-15
期刊：
影响因子：
--
通讯作者：
Luo X
中科院分区：
文献类型：
--
作者：
Bryant J;Lerret NM;Wang JJ;Kang HK;Tasch J;Zhang Z;Luo X
我们以前已经表明，预先输注的凋亡供体脾细胞处理的化学交联剂乙基碳二亚胺（ECDI-SPs）诱导长期同种异体移植物存活在完全MHC不匹配模型的同种异体胰岛和心脏移植。髓源性抑制细胞（MDSC）在ECDI-SP提供的移植物保护中的作用尚不清楚。在这项研究中，我们证明了输注ECDI-SP增加了脾脏中两种CD 11b+细胞群，其表型类似于单核细胞样（CD 11b + Ly 6CHI）和粒细胞样（CD 11b + Gr 1HI）MDSC。这两个群体在体外抑制T细胞增殖，并在体内运输至心脏同种异体移植物，以通过抑制局部CD 8 T细胞积聚以及潜在地还通过诱导和归巢调节性T细胞来介导其保护。重要的是，用ECDI-SP重复处理诱导CD 11b + Gr 1HI细胞产生高水平的IFN-γ，并通过表达更高水平的下游效应分子ido和nos 2来表现出对IFN-γ的增强的应答性。因此，IFN-γ的中和完全消除了该群体的抑制能力。我们的结论是，供体ECDI-SP诱导了两个群体的MDSC的扩增，这两个群体对同种异体移植物保护很重要，部分由内在IFN-γ依赖机制介导。这种形式的抢先供体凋亡细胞输注对于MDSC用于移植耐受诱导的治疗性操作具有显著的潜力。
We have previously shown that preemptive infusion of apoptotic donor splenocytes treated with the chemical cross-linker ethylcarbodiimide (ECDI-SPs) induces long-term allograft survival in full MHC-mismatched models of allogeneic islet and cardiac transplantation. The role of myeloid derived suppressor cells (MDSCs) in the graft protection provided by ECDI-SPs is unclear. In this study, we demonstrate that infusions of ECDI-SPs increase two populations of CD11b+ cells in the spleen that phenotypically resemble monocytic-like (CD11b+Ly6CHI) and granulocytic-like (CD11b+Gr1HI) MDSCs. Both populations suppress T cell proliferation in vitro, and traffic to the cardiac allografts in vivo to mediate their protection via inhibition of local CD8 T cell accumulation and potentially also via induction and homing of regulatory T cells. Importantly, repeated treatments with ECDI-SPs induce the CD11b+Gr1HI cells to produce a high level of IFN-γ and to exhibit an enhanced responsiveness to IFN-γ by expressing higher levels of downstream effector molecules ido and nos2. Consequently, neutralization of IFN-γ completely abolishes the suppressive capacity of this population. We conclude that donor ECDI-SPs induce the expansion of two populations of MDSCs important for allograft protection mediated in part by intrinsic IFN-γ dependent mechanisms. This form of preemptive donor apoptotic cell infusions has significant potential for the therapeutic manipulation of MDSCs for transplant tolerance induction.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
3.7
作者：
Fridlender ZG;Sun J;Mishalian I;Singhal S;Cheng G;Kapoor V;Horng W;Fridlender G;Bayuh R;Worthen GS;Albelda SM
通讯作者：
Albelda SM
DOI：
10.1111/j.1600-6143.2012.04203.x
发表时间：
2012-11
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：
Chen G;Kheradmand T;Bryant J;Wang S;Tasch J;Wang JJ;Zhang Z;Luo X
通讯作者：
Luo X
影响因子：
82.9
作者：
Nagaraj, Srinivas;Gupta, Kapil;Gabrilovich, Dmitry I.
通讯作者：
Gabrilovich, Dmitry I.
影响因子：
20.3
作者：
Movahedi, Kiavash;Guilliams, Martin;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.