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单克隆IgG抗体影响体内淋巴细胞的迁移模式。

Monoclonal IgG antibodies influence the migration patterns of lymphocytes in vivo.

作者信息

Yousaf N, Williams B D

机构信息

Department of Rheumatology, University of Wales College of Medicine, Cardiff, UK.

出版信息

Int Arch Allergy Immunol. 1999 Jan;118(1):59-66. doi: 10.1159/000024032.

Abstract

Monoclonal antibodies (MoAb) are useful therapeutic agents for the treatment of a variety of human disorders, although the effector mechanisms responsible for the outcome of an efficient immunotherapy remain unclear. This study was designed to address the early effects of MoAb on the migration patterns of lymphocytes in vivo. The clearance profiles and tissue distribution of 111In-labelled rat lymph node cells were examined in both normal and decomplemented allogeneic and semi-allogeneic recipients pre-injected with IgG2b (R3/13) or IgG2a (R2/15S) MoAb directed against the RT1Aa, the classical class I major histocompatibility complex antigen of the DA rat. Both MoAb were equally effective in not only augmenting the removal of DA and (DA x PVG)F1 cells from the circulation and promoting their subsequent localization within the liver but also causing a significant degree of cell lysis during the early phase of cell clearance, even in decomplemented recipients. Although R3/13 and R2/15S are known to target erythrocytes differently in normal and cobra venom factor (CVF)-treated animals, no differences were observed in the migration behaviour of lymph node cells in allogeneic or semi-allogeneic hosts pre-injected with the same MoAb. Since rat lymphocytes express a much higher level of the RT1Aa antigen as compared with erythrocytes, we could not exclude a possible role of residual complement components in the circulation of CVF-treated rats that may have accounted for the observed antibody-dependent effects on target lymphocytes. On the basis of these findings we believe that the design and methodology employed in our present experimental opsonization system were inadequate to define clearly the mechanisms responsible for antibody-mediated removal and destruction of target lymphocytes in vivo.

摘要

单克隆抗体(MoAb)是治疗多种人类疾病的有效治疗剂,尽管有效免疫治疗结果所涉及的效应机制仍不清楚。本研究旨在探讨MoAb对体内淋巴细胞迁移模式的早期影响。在预先注射针对DA大鼠经典I类主要组织相容性复合体抗原RT1Aa的IgG2b(R3/13)或IgG2a(R2/15S)MoAb的正常、补体灭活的同种异体和半同种异体受体中,检测了111In标记的大鼠淋巴结细胞的清除情况和组织分布。两种MoAb不仅在增强从循环中清除DA和(DA×PVG)F1细胞以及促进它们随后在肝脏中的定位方面同样有效,而且在细胞清除的早期阶段即使在补体灭活的受体中也会引起显著程度的细胞裂解。尽管已知R3/13和R2/15S在正常和眼镜蛇毒因子(CVF)处理的动物中对红细胞的靶向作用不同,但在预先注射相同MoAb的同种异体或半同种异体宿主中,未观察到淋巴结细胞迁移行为的差异。由于与红细胞相比,大鼠淋巴细胞表达的RT1Aa抗原水平要高得多,我们不能排除CVF处理大鼠循环中残留补体成分可能发挥的作用,这可能解释了观察到的对靶淋巴细胞的抗体依赖性效应。基于这些发现,我们认为我们目前实验调理系统中所采用的设计和方法不足以明确体内抗体介导的靶淋巴细胞清除和破坏机制。

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