Anti-mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice.
Anti-mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice.
复制标题
抗小鼠 CD154 抗体治疗可促进混合异种大鼠造血嵌合体的产生，预防消耗性疾病并延长小鼠异种移植物的存活时间。
DOI：
10.1111/j.1399-3089.2006.00290.x
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发表时间：
2006
影响因子：
3.9
通讯作者：
Rossini,AldoA
中科院分区：
文献类型：
--
作者：
Masaki,Hideyuki;Appel,MichaelC;Leahy,Linda;Leif,Jean;Paquin,Linda;Shultz,LeonardD;Mordes,JohnP;Greiner,DaleL;Rossini,AldoA
Masaki H, Appel MC, Leahy L, Leif J, Paquin L, Shultz LD, Mordes JP, Greiner DL, Rossini AA。抗小鼠CD154抗体治疗促进了混合异种大鼠造血嵌合的产生，防止了消耗性疾病，延长了小鼠异种移植物的存活时间。
异种移植2006;13: 224 - 232。摘要：背景：诱导异种造血嵌合是克服宿主对异种移植物反应的一种有吸引力的方法，但建立异种造血嵌合需要对受体进行严格的清髓调节。本研究的目的是确定共刺激阻断是否会促进辐照条件下和谐受体的嵌合和异种移植物耐受性。方法：将Wistar Furth大鼠骨髓（BM）细胞注射到辐照条件下的C57BL/6小鼠体内，同时或不同时注射抗小鼠CD154单克隆抗体（mAb）。用流式细胞术定量嵌合，并将WF大鼠皮肤和胰岛移植给小鼠。结果：阻断CD40-CD154相互作用促进了600 cGy辐照小鼠异种嵌合的建立。在700 cGy小鼠中，不需要Anti - CD154 mAb来建立嵌合。然而，接受700 cGy辐射但未接受抗CD154单抗治疗的小鼠，无论嵌合的发展如何，都会出现“移植物抗宿主病（GVHD）样”消耗综合征并死亡。用辐照和抗CD154单抗治疗建立的异种嵌合体表现出延长皮肤和在许多情况下永久胰岛移植的生存时间。嵌合不稳定，最终在大多数受体中消失。即使在嵌合的小鼠中，皮肤异种移植物也被排斥，而大多数胰岛异种移植物存活到观察期结束。结论：阻断宿主CD40-CD154相互作用有助于异种嵌合的建立，防止疾病和死亡的发生。嵌合可以延长异种移植物的存活时间，但这种方式产生的嵌合随着时间的推移不稳定。皮肤异种移植物最终会被排斥，而大多数胰岛异种移植物能长期存活，甚至可能永久存活。
Masaki H, Appel MC, Leahy L, Leif J, Paquin L, Shultz LD, Mordes JP, Greiner DL, Rossini AA. Anti‐mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice.
Xenotransplantation 2006; 13: 224–232. © Blackwell Munksgaard, 2006Abstract:Background:The induction of xenogeneic hematopoietic chimerism is an attractive approach for overcoming the host response to xenografts, but establishing xenogeneic chimerism requires severe myeloablative conditioning of the recipient. The goal of this study was to determine if co‐stimulation blockade would facilitate chimerism and xenograft tolerance in irradiation‐conditioned concordant recipients.Methods:Wistar Furth rat bone marrow (BM) cells were injected into irradiation‐conditioned C57BL/6 mice with or without co‐administration of anti‐mouse CD154 monoclonal antibody (mAb). Chimerism was quantified by flow cytometry, and mice were transplanted with WF rat skin and islet xenografts.Results:Blockade of CD40–CD154 interaction facilitated establishment of xenogeneic chimerism in mice conditioned with 600 cGy irradiation. Anti‐CD154 mAb was not required for establishment of chimerism in mice treated with 700 cGy. However, mice irradiated with 700 cGy but not treated with anti‐CD154 mAb developed a “graft‐versus‐host disease (GVHD)‐like” wasting syndrome and died, irrespective of their development of chimerism. Xenogeneic chimeras established with irradiation and anti‐CD154 mAb treatment exhibited prolonged skin and, in many cases, permanent islet xenograft survival. Chimerism was unstable and eventually lost in most recipients. Skin xenografts were rejected even in mice that remained chimeric, whereas most islet xenografts survived to the end of the observation period.Conclusions:Blockade of host CD40–CD154 interaction facilitates the establishment of xenogeneic chimerism and prevents wasting disease and death. Chimerism permits prolonged xenograft survival, but chimerism generated in this way is unstable over time. Skin xenografts are eventually rejected, whereas most islet xenografts survive long term and perhaps permanently.