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大鼠-小鼠辐射嵌合体:抗体介导的移植物抗宿主反应的特征

Rat-mouse radiation chimeras: characterization of an antibody-mediated graft-vs-host reaction.

作者信息

Kateley J R, Gengozian N

出版信息

J Immunol. 1975 Jan;114(1 Pt 1):125-32.

PMID:234495
Abstract

A modification of the Jerne hemolysis-in-agar technique was used to demonstrate antibody-mediated graft-vs-host (GvH) hemolytic activity in lymphoid tissues of rat-mouse radiation chimeras. Initial foci of hemolytic activity were detected on the 3rd day in spleens of lethally x-irradiated mice infused with rat spleen cells (950 R-RSp chimeras). The peak of GvH foci response occurred near the end of the 1st week when 70% of 950 R-RSp chimera spleens examined contained an average of 18 to 21 foci per spleen. GvH hemolytic activity was also detected in mice reconstituted with rat bone marrow (950 R-RBM chimeras); however, only 40% of these chimeras contained splenic foci (nine foci per spleen) on day 8, the peak day of response. Mesenteric lymph nodes from 950 R-RSp chimeras, but not 950 R-RBM chimeras, also contained GvH hemolytic foci. Specificity experiments demonstrated that the GvH hemolytic reaction could be inhibited with rabbit anti-rat IgM serum and host (C3BF) antigenic cell fragments. Indirect (IgG) hemolytic activity was also observed in spleens of 950 R-RSp chimeras 6 to 10 days after treatment. At least 90% of indirect foci appeared coincident with direct foci. Rat IgM and IgG containing cells beneath hemolytic foci were observed by combining the fluorescent antibody and foci techniques. To determine whether the foci response reflects and in vivo sensitization of donor cells, spleen cell transfer experiments were done. The results indicate that spleen cells from 950 R-RSp chimeras were more effective in acelerating mortality and anemia and induced a higher incidence of Coomb's positive red cells in lethally irradiated isogeneic recipients than spleen cells from 950 R-RBM chimeras; spleen cells from either chimera were more effective in accelerating GvH indices than spleen and marrow cells from normal rats.

摘要

采用改良的耶尔恩琼脂溶血技术,以证明大鼠 - 小鼠辐射嵌合体淋巴组织中抗体介导的移植物抗宿主(GvH)溶血活性。在注入大鼠脾细胞的致死性X射线照射小鼠(950R - RSp嵌合体)的脾脏中,于第3天检测到溶血活性的初始病灶。GvH病灶反应的峰值出现在第1周快结束时,此时检查的950R - RSp嵌合体脾脏中70%平均每个脾脏含有18至21个病灶。在用大鼠骨髓重建的小鼠(950R - RBM嵌合体)中也检测到GvH溶血活性;然而,在反应峰值日第8天,这些嵌合体中只有40%的脾脏含有病灶(每个脾脏9个病灶)。950R - RSp嵌合体的肠系膜淋巴结含有GvH溶血病灶,但950R - RBM嵌合体的则没有。特异性实验表明,GvH溶血反应可被兔抗大鼠IgM血清和宿主(C3BF)抗原性细胞片段抑制。在处理后6至10天内,950R - RSp嵌合体的脾脏中也观察到间接(IgG)溶血活性。至少90%的间接病灶与直接病灶同时出现。通过结合荧光抗体和病灶技术,观察到溶血病灶下方含有大鼠IgM和IgG的细胞。为了确定病灶反应是否反映供体细胞的体内致敏作用,进行了脾细胞转移实验。结果表明,与950R - RBM嵌合体来源的脾细胞相比,950R - RSp嵌合体来源的脾细胞在加速致死性照射的同基因受体的死亡率和贫血方面更有效,并且诱导Coomb's阳性红细胞的发生率更高;两种嵌合体来源的脾细胞在加速GvH指数方面比正常大鼠的脾细胞和骨髓细胞更有效。

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