Inhibition of resistance to hemopoietic allo‐grafts in granulocyte colony‐stimulating factor transgenic mice

Inhibition of resistance to hemopoietic allo‐grafts in granulocyte colony‐stimulating factor transgenic mice
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粒细胞集落刺激因子转基因小鼠对造血同种异体移植物抗性的抑制

DOI:
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发表时间:
1996
影响因子:
5.4
通讯作者:
J. Fujimoto
J. Fujimoto
中科院分区:
医学3区
文献类型:
--
作者:
Y. Kokai;H. Kaneko;Kooh Izuka;A. Matsuura;J. Fujimoto

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移植的同种异体骨髓细胞往往不能移植到受致死性辐射的宿主体内。这种现象被称为对同种异体骨髓移植物的抗性或同种异体抗性,有充分的文献记载,尽管其机制尚不清楚。将主要组织相容性复合体不同的同种异体骨髓细胞移植到粒细胞集落刺激因子(G-CSF)转基因小鼠中,显示出供体来源的脾集落(CFU-S),并产生稳定的同种异体嵌合体,存活率极佳(40天内100%,120天内89%)。在相同的实验条件下,所有同窝对照均未显示CFU-S,并在骨髓移植后不久死亡。因此,这种转基因小鼠对同种异体骨髓细胞的抗性似乎严重受损。针对G-CSF的中和抗体在G-CSF转基因小鼠中恢复了同种异体抗性,并且在非转基因受体中使用微渗透泵给予重组G-CSF后可诱导CFU-S,这表明该细胞因子水平升高对于抑制同种异体抗性很重要。因此,发现G-CSF在对骨髓移植物的同种异体抗性中起作用,并且G-CSF转基因小鼠提供了研究抗性抑制的有用模型。在实验和临床环境中,抑制同种异体耐药性可能有助于制备同种异体骨髓嵌合体。
Transplanted allogeneic marrow cells often fail to engraft in a lethally irradiated host. This phenomenon, termed resistance to allogeneic marrow grafts or allo‐resistance, is well documented, although its mechanism is not yet understood. Transplantation of major histocompatibility complex disparate allogeneic marrow cells into mice transgenic for granulocyte colony‐stimulating factor (G‐CSF) showed donor‐derived spleen colonies (CFU‐S) and resulted in stable allogeneic chimerism with excellent survival (100% up to 40 days and 89% up to 120 days). Under the same experimental conditions, all the littermate controls failed to show CFU‐S and died shortly after marrow transplantation. Thus, resistance to allogeneic marrow cells appeared to be severely impaired in this transgenic mouse. The observation that neutralizing antibody against G‐CSF restored allo‐resistance in G‐CSF transgenic mice and that CFU‐S was inducible upon administration of recombinant G‐CSF using a mini‐osmotic pump in non‐transgenic recipients, suggests that an elevated level of this cytokine is important for the inhibition of allo‐resistance. Thus, G‐CSF was found to play a role in allogeneic resistance to marrow grafts and the G‐CSF‐transgenic mice provide a useful model to study the inhibition of the resistance. The inhibition of allo‐resistance may be useful in preparing allogeneic bone marrow chimeras in both experimental and clinical settings.
DOI: 10.4049/jimmunol.142.10.3423
发表时间: 1989-05
影响因子: 4.4
作者:
B. Yankelevich;C. Knobloch;M. Nowicki;G. Dennert
通讯作者: B. Yankelevich;C. Knobloch;M. Nowicki;G. Dennert
DOI: --
发表时间: 1992
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Kikly,K;Dennert,G
通讯作者: Dennert,G