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用单克隆抗体调节日本血吸虫肺虫卵肉芽肿

Modulation of Schistosoma japonicum pulmonary egg granulomas with monoclonal antibodies.

作者信息

Sidner R A, Carter C E, Colley D G

出版信息

Am J Trop Med Hyg. 1987 Mar;36(2):361-70. doi: 10.4269/ajtmh.1987.36.361.

DOI:10.4269/ajtmh.1987.36.361
PMID:3103476
Abstract

We have examined the ability of various Schistosoma japonicum egg antigens to sensitize mice for subsequent secondary pulmonary egg granuloma formation. Further, we produced monoclonal antibodies (Mabs) specific for egg antigens and evaluated their abilities to modulate pulmonary granuloma formation and inhibit soluble egg antigen (SEA)-stimulated lymphocyte blastogenesis. A homogeneous, 140 Kd egg glycoprotein, SJe; 140-GP was nearly as effective as intact eggs in sensitizing for egg-focused pulmonary granuloma formation, while SEA, or the heterogeneous immunoaffinity (IA)-purified C10 antigens were ineffective. The in vivo administration of chronic infection serum (CIS) or Mabs reactive with SJe; 140-GP, to egg-sensitized/egg-challenged mice, modulated pulmonary granuloma formation. Two of these modulatory SJe; 140-GP-specific Mabs (1 A1-1 or 14B3-8), an IgG1, and an IgG3, respectively, did not alter the responses of SEA-stimulated lymph node cells from mice with acute or chronic schistosomiasis japonica. In contrast, another SJe; 140-GP-specific IgG3 Mab (7A6-5), CIS, immunoaffinity purified anti-SEA from CIS, or the non-SEA-binding fraction of CIS, all resulted in dose-related inhibition of SEA-induced proliferation. These data confirm the antibody-driven nature of some immunoregulatory networks in murine schistosomiasis japonica, and extend these observations to include certain Mabs. The immunogenic nature of SJe; 140-GP, and the modulatory and inhibitory activities of Mabs specific for this glycoprotein, indicate it may play a central role in granuloma formation and modulation in this infection.

摘要

我们研究了日本血吸虫虫卵的各种抗原使小鼠致敏以形成后续继发性肺部虫卵肉芽肿的能力。此外,我们制备了针对虫卵抗原的单克隆抗体(Mab),并评估了它们调节肺部肉芽肿形成以及抑制可溶性虫卵抗原(SEA)刺激的淋巴细胞增殖的能力。一种均一的140Kd虫卵糖蛋白SJe;140 - GP在使小鼠致敏以形成虫卵聚焦性肺部肉芽肿方面几乎与完整虫卵一样有效,而SEA或异质性免疫亲和(IA)纯化的C10抗原则无效。向虫卵致敏/虫卵攻击的小鼠体内给予慢性感染血清(CIS)或与SJe;140 - GP反应的Mab,可调节肺部肉芽肿的形成。其中两种调节性的SJe;140 - GP特异性Mab(1A1 - 1或14B3 - 8),分别为IgG1和IgG3,并未改变急性或慢性日本血吸虫病小鼠SEA刺激的淋巴结细胞的反应。相比之下,另一种SJe;140 - GP特异性IgG3 Mab(7A6 - 5)、CIS、从CIS中免疫亲和纯化的抗SEA或CIS的非SEA结合部分,均导致SEA诱导的增殖呈剂量依赖性抑制。这些数据证实了小鼠日本血吸虫病中某些免疫调节网络的抗体驱动性质,并将这些观察结果扩展至包括某些Mab。SJe;140 - GP的免疫原性以及针对该糖蛋白的Mab的调节和抑制活性表明,它可能在这种感染的肉芽肿形成和调节中起核心作用。

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