Selective Blockade of IL-15 by Soluble IL-15 Receptor α-Chain Enhances Cardiac Allograft Survival1
Selective Blockade of IL-15 by Soluble IL-15 Receptor α-Chain Enhances Cardiac Allograft Survival1
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可溶性 IL-15 受体 α 链选择性阻断 IL-15 可增强同种异体心脏移植物的存活率1
DOI：
10.4049/jimmunol.165.6.3444
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
J. Bradley
中科院分区：
文献类型：
--
作者：
X. Smith;E. Bolton;H. Ruchatz;Xiao;F. Liew;J. Bradley
IL-15是一种与IL-2具有许多功能相似性的T细胞生长因子，最近被证明存在于组织和器官同种异体移植物中，导致IL-15可能有助于移植物排斥反应。在这里，我们报告了IL-15拮抗剂（小鼠IL-15R α-链的可溶性片段）在小鼠实验模型中的体内使用，以研究IL-15对完全血管化的异体心脏移植排斥反应的贡献。将小鼠IL-15Rα -链可溶性片段（sIL-15Rα）给予CBA/Ca （H-2k）受体10天，完全阻止了轻微组织相容性复合物不匹配B10的排斥反应。BR （H-2k）心脏移植（中位生存时间（MST）为100天，而对照组的MST为10天）并导致供者特异性免疫耐受状态。单独使用sIL-15Rα治疗CBA/Ca受体对完全mhc错配的BALB/c （H-2d）心脏移植物的存活只有适度的影响。然而，sIL-15Rα与单剂量非耗损性抗cd4单抗（YTS 177.9）联合使用可延迟移植物的单核细胞浸润，并显著延长移植物存活时间（MST为60天，而单独使用抗cd4治疗的MST为20天）。在体外，脾脏细胞增殖和IFN-γ产生减少，同时移植物存活时间延长，而CTL和同种异体抗体水平与单独给予抗cd4单抗的动物相似。这些发现表明，IL-15在血管化器官移植的排斥反应中起重要作用，IL-15拮抗剂可能在预防同种异体移植排斥反应中具有治疗价值。
IL-15 is a T cell growth factor that shares many functional similarities with IL-2 and has recently been shown to be present in tissue and organ allografts, leading to speculation that IL-15 may contribute to graft rejection. Here, we report on the in vivo use of an IL-15 antagonist, a soluble fragment of the murine IL-15R α-chain, to investigate the contribution of IL-15 to the rejection of fully vascularized cardiac allografts in a mouse experimental model. Administration of soluble fragment of the murine IL-15R α-chain (sIL-15Rα) to CBA/Ca (H-2k) recipients for 10 days completely prevented rejection of minor histocompatibility complex-mismatched B10.BR (H-2k) heart grafts (median survival time (MST) of >100 days vs MST of 10 days for control recipients) and led to a state of donor-specific immunologic tolerance. Treatment of CBA/Ca recipients with sIL-15Rα alone had only a modest effect on the survival of fully MHC-mismatched BALB/c (H-2d) heart grafts. However, administration of sIL-15Rα together with a single dose of a nondepleting anti-CD4 mAb (YTS 177.9) delayed mononuclear cell infiltration of the grafts and markedly prolonged graft survival (MST of 60 days vs MST of 20 days for treatment with anti-CD4 alone). Prolonged graft survival was accompanied in vitro by reduced proliferation and IFN-γ production by spleen cells, whereas CTL and alloantibody levels were similar to those in animals given anti-CD4 mAb alone. These findings demonstrate that IL-15 plays an important role in the rejection of a vascularized organ allograft and that antagonists to IL-15 may be of therapeutic value in preventing allograft rejection.
使用拮抗剂 IL-15 突变体/Fc gamma2a 蛋白靶向 IL-15 受体可阻断迟发型超敏反应。
DOI：
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发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim,YS;Maslinski,W;Zheng,XX;Stevens,AC;Li,XC;Tesch,GH;Kelley,VR;Strom,TB
通讯作者：
Strom,TB
影响因子：
4.4
作者：
Xian Chang Li;Prabir Roy-Chaudhury;Wayne W. Hancock;R. Manfro;Martin S. Zand;Yongsheng Li;X. Zheng;Peter W. Nickerson;Jürg Steiger;T. Malek;Terry B. Strom
通讯作者：
Xian Chang Li;Prabir Roy-Chaudhury;Wayne W. Hancock;R. Manfro;Martin S. Zand;Yongsheng Li;X. Zheng;Peter W. Nickerson;Jürg Steiger;T. Malek;Terry B. Strom
阻断细胞因子受体的共同伽马链可诱导 T 细胞凋亡和胰岛同种异体移植物的长期存活。
DOI：
10.4049/jimmunol.164.3.1193
发表时间：
2000
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li,XC;Ima,A;Li,Y;Zheng,XX;Malek,TR;Strom,TB
通讯作者：
Strom,TB