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体内给予白细胞介素-2受体特异性单克隆抗体对小鼠急性移植物抗宿主反应的影响。

Effects of in-vivo administration of a monoclonal antibody specific for the interleukin-2 receptor on the acute graft-versus-host reaction in mice.

作者信息

Volk H D, Brocke S, Osawa H, Diamantstein T

出版信息

Clin Exp Immunol. 1986 Oct;66(1):126-31.

PMID:3100116
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1542657/
Abstract

Parental strain T lymphocyte injected into F1 mice respond to allogeneic MHC antigens and so induce the symptoms of a graft-versus-host reaction (GVHR). We have measured the local GVHR by the popliteal lymph node assay, and showed the suppression of the local GVHR in mice by treatment with the monoclonal antibody (MoAb) AMT-13 which is specific against the interleukin 2 (IL-2) receptor on activated mouse lymphocytes. The inhibitory effect of the AMT-13 administration was comparable with the suppression of the local GVHR by treatment with L3T4, an MoAb directed against the T helper subset. The L3T4 administration caused a dramatic decrease in the proportion of the cells with the L3T4 phenotype in the circulation and a marginal reduction of these cells in the lymph nodes. In contrast, the AMT-13 treated mice showed no changes in the distribution of the T lymphocyte subsets besides those in the GVHR-stimulated lymph nodes. Obviously, only the small subset of antigen-activated IL-2 receptor-bearing lymphocytes was influenced by treatment with AMT-13. MoAb directed against antigens whose expression is restricted to activated lymphocytes, such as the IL-2 receptor, might become useful for a short term immunosuppression with limited side effects.

摘要

将亲代品系T淋巴细胞注射到F1小鼠体内会对同种异体MHC抗原产生反应,从而引发移植物抗宿主反应(GVHR)的症状。我们通过腘淋巴结试验测定了局部GVHR,并显示用针对活化小鼠淋巴细胞上白细胞介素2(IL-2)受体的单克隆抗体(MoAb)AMT-13处理可抑制小鼠的局部GVHR。AMT-13给药的抑制作用与用针对T辅助亚群的MoAb L3T4处理对局部GVHR的抑制作用相当。给予L3T4会导致循环中具有L3T4表型的细胞比例急剧下降,并且淋巴结中这些细胞略有减少。相比之下,除了在GVHR刺激的淋巴结中,AMT-13处理的小鼠T淋巴细胞亚群的分布没有变化。显然,只有一小部分抗原活化的携带IL-2受体的淋巴细胞受到AMT-13处理的影响。针对其表达仅限于活化淋巴细胞的抗原(如IL-2受体)的单克隆抗体可能对短期免疫抑制有用且副作用有限。

相似文献

1
Effects of in-vivo administration of a monoclonal antibody specific for the interleukin-2 receptor on the acute graft-versus-host reaction in mice.体内给予白细胞介素-2受体特异性单克隆抗体对小鼠急性移植物抗宿主反应的影响。
Clin Exp Immunol. 1986 Oct;66(1):126-31.
2
Suppression of the local graft-vs.-host reaction in rats by treatment with a monoclonal antibody specific for the interleukin 2 receptor.用针对白细胞介素2受体的单克隆抗体治疗抑制大鼠局部移植物抗宿主反应。
Eur J Immunol. 1986 Oct;16(10):1309-12. doi: 10.1002/eji.1830161020.
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J Immunol. 1987 Feb 15;138(4):1038-41.
5
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J Immunol. 1988 Apr 15;140(8):2600-8.
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The therapeutic efficacy of an anti-IL-2 receptor monoclonal antibody correlates with an increase in serum soluble IL-2 receptor levels.抗白细胞介素-2受体单克隆抗体的治疗效果与血清可溶性白细胞介素-2受体水平的升高相关。
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A rat monoclonal antibody that binds specifically to mouse T lymphoblasts and inhibits IL 2 receptor functions: a putative anti-IL 2 receptor antibody.一种能特异性结合小鼠T淋巴母细胞并抑制白细胞介素2受体功能的大鼠单克隆抗体:一种假定的抗白细胞介素2受体抗体。
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Specific immunosuppressive therapy by monoclonal anti-IL 2 receptor antibody and its synergistic action with cyclosporin.单克隆抗白细胞介素-2受体抗体的特异性免疫抑制疗法及其与环孢素的协同作用。
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Alloreactive lymphocytes from T cell receptor (beta-chain) transgenic mice do not mediate a graft-versus-host reaction.来自T细胞受体(β链)转基因小鼠的同种反应性淋巴细胞不会介导移植物抗宿主反应。
J Immunol. 1991 Feb 15;146(4):1130-3.

引用本文的文献

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Advances in interleukin 2 receptor targeted treatment.白细胞介素2受体靶向治疗的进展
Ann Rheum Dis. 2000 Nov;59 Suppl 1(Suppl 1):i109-14. doi: 10.1136/ard.59.suppl_1.i109.
2
The therapeutic efficacy of an anti-IL-2 receptor monoclonal antibody correlates with an increase in serum soluble IL-2 receptor levels.抗白细胞介素-2受体单克隆抗体的治疗效果与血清可溶性白细胞介素-2受体水平的升高相关。
Clin Exp Immunol. 1989 Apr;76(1):121-5.
3
A humanized antibody that binds to the interleukin 2 receptor.一种与白细胞介素2受体结合的人源化抗体。
Proc Natl Acad Sci U S A. 1989 Dec;86(24):10029-33. doi: 10.1073/pnas.86.24.10029.

本文引用的文献

1
Studies on the interleukin-2 receptor, its generation and dynamics using monoclonal anti-interleukin-2 receptor antibodies.利用抗白细胞介素-2受体单克隆抗体对白细胞介素-2受体及其产生和动态变化的研究。
Mol Immunol. 1984 Dec;21(12):1229-36. doi: 10.1016/0161-5890(84)90015-4.
2
A rat monoclonal antibody that binds specifically to mouse T lymphoblasts and inhibits IL 2 receptor functions: a putative anti-IL 2 receptor antibody.一种能特异性结合小鼠T淋巴母细胞并抑制白细胞介素2受体功能的大鼠单克隆抗体:一种假定的抗白细胞介素2受体抗体。
J Immunol. 1984 May;132(5):2445-50.
3
Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Clinical results and effect on circulating T lymphocytes.
Transplantation. 1984 Nov;38(5):469-74. doi: 10.1097/00007890-198411000-00005.
4
Effects of in vivo administration of monoclonal antibodies specific for human T cell subpopulations on the immune system in a rhesus monkey model.在恒河猴模型中,体内给予针对人类T细胞亚群的单克隆抗体对免疫系统的影响。
Transplantation. 1983 Jun;35(6):521-6. doi: 10.1097/00007890-198306000-00001.
5
Murine monoclonal anti-T cell antibodies for treatment of steroid-resistant acute graft-versus-host disease.用于治疗类固醇难治性急性移植物抗宿主病的鼠单克隆抗T细胞抗体。
Hum Immunol. 1984 Jan;9(1):21-35. doi: 10.1016/0198-8859(84)90004-1.
6
The immunosuppressive effect of monoclonal anti-Lyt-1.1 antibodies in vivo.单克隆抗Lyt-1.1抗体在体内的免疫抑制作用。
Eur J Immunol. 1981 Dec;11(12):1005-12. doi: 10.1002/eji.1830111211.
7
Fatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody.用鼠抗T细胞抗体治疗急性移植物抗宿主病后,与供体B细胞相关的致命性EB病毒增殖。
Ann Intern Med. 1984 Sep;101(3):310-5. doi: 10.7326/0003-4819-101-3-310.
8
Effect of in vivo administration of Lyt antibodies. Lyt phenotype of T cells in lymphoid tissues and blocking of tumor rejection.体内给予Lyt抗体的效果。淋巴组织中T细胞的Lyt表型及肿瘤排斥反应的阻断。
J Exp Med. 1985 Feb 1;161(2):345-55. doi: 10.1084/jem.161.2.345.
9
Therapy with monoclonal antibody to interleukin 2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats.用白细胞介素2受体单克隆抗体进行治疗可使抑制性T细胞免受影响,并预防或逆转大鼠的急性同种异体移植排斥反应。
Proc Natl Acad Sci U S A. 1986 Apr;83(8):2624-7. doi: 10.1073/pnas.83.8.2624.