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对IFN-γ特异性抗犬细胞因子单克隆抗体的特性分析:抗IFN-γ对肾移植排斥反应的影响

Characterization of anti-canine cytokine monoclonal antibodies specific for IFN-gamma: effect of anti-IFN-gamma on renal transplant rejection.

作者信息

Fuller L, Carreno M, Esquenazi V, Zucker K, Zheng S, Roth D, Burke G, Nery J, Asthana D, Olson L

机构信息

Department of Surgery, University of Miami School of Medicine, Florida.

出版信息

Tissue Antigens. 1994 Mar;43(3):163-9. doi: 10.1111/j.1399-0039.1994.tb02317.x.

DOI:10.1111/j.1399-0039.1994.tb02317.x
PMID:8091415
Abstract

Two murine monoclonal antibodies specific for IFN-gamma, ADI-1, and ADI-23 (both IgG1 kappa), were generated in BALB/c mice. The ADI-1 exhibited a higher avidity for canine rIFN-gamma than for nIFN-gamma and human rIFN-gamma. In contrast, the ADI-23 showed equal avidity for the three IFN-gamma preparations. The anti-canine IFN-gamma mAb did not bind to mouse and rat rIFN-gamma. The ADI-1, and ADI-23 mAb were also tested for binding to human rTFN-alpha and, contrary to our expectations, it was found that ADI-23 showed significant binding to human rTFN-alpha and rIFN-gamma, in contrast to ADI-1. Both anti-canine IFN-gamma mAb stained 48-h PHA-induced dog lymphoblasts. A two-site mAb ELISA was developed, which was linear in the range of 7-500 ng of canine rIFN-gamma, which indicated that the two mAb detected non-overlapping epitopes on the canine rIFN-gamma molecule. We studied the effect of ADI-1 on the prolongation of canine renal allografts. Recipients of kidney allografts, that were treated with ADI-1 by continuous arterial infusion, were prolonged to 22 and 25 days, compared to 9 and 13 days for animals given the IgG1 isotype control.

摘要

在BALB/c小鼠中产生了两种对干扰素-γ具有特异性的鼠单克隆抗体ADI-1和ADI-23(均为IgG1 κ)。ADI-1对犬重组干扰素-γ的亲和力高于对天然干扰素-γ和人重组干扰素-γ的亲和力。相比之下,ADI-23对这三种干扰素-γ制剂的亲和力相同。抗犬干扰素-γ单克隆抗体不与小鼠和大鼠重组干扰素-γ结合。还检测了ADI-1和ADI-23单克隆抗体与人重组肿瘤坏死因子-α的结合情况,与我们的预期相反,发现ADI-23与人类重组肿瘤坏死因子-α和重组干扰素-γ有显著结合,而ADI-1则不然。两种抗犬干扰素-γ单克隆抗体均能对48小时PHA诱导的犬淋巴母细胞进行染色。开发了一种双位点单克隆抗体酶联免疫吸附测定法,该方法在7 - 500 ng犬重组干扰素-γ范围内呈线性,这表明这两种单克隆抗体检测到犬重组干扰素-γ分子上不重叠的表位。我们研究了ADI-1对犬肾同种异体移植存活期延长的影响。通过持续动脉输注用ADI-1治疗的肾同种异体移植受者的存活期延长至22天和25天,而给予IgG1同型对照的动物存活期为9天和13天。

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Characterization of anti-canine cytokine monoclonal antibodies specific for IFN-gamma: effect of anti-IFN-gamma on renal transplant rejection.对IFN-γ特异性抗犬细胞因子单克隆抗体的特性分析:抗IFN-γ对肾移植排斥反应的影响
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