Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells
Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells
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DOI：
10.1046/j.1365-2249.1996.55764.x
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发表时间：
1996-06-01
影响因子：
4.6
通讯作者：
Nobunaga, M
中科院分区：
文献类型：
--
作者：
Ezaki, I;Okada, M;Nobunaga, M
为了研究类风湿因子（RF）的体内作用，检查了施用人单克隆（m）IgM-RF和IgG-RF对小鼠关节炎发展的影响。向用II型胶原（CII）免疫的小鼠中施用人mRF显著增强了临床评分和爪肿胀。在接受RF的两组中，关节炎关节疾病的严重程度显著增强，淋巴细胞显著浸润，滑膜增殖，血管翳形成和关节软骨破坏（RF增强型关节炎）。在这些RF增强的关节炎小鼠中的一些中也观察到皮肤溃疡，而在没有mRF的CII免疫小鼠中没有观察到这样的体征。IgM-RF和IgG-RF都增加了循环中的CII特异性IgG抗体，关节炎的严重程度与高滴度抗CII抗体的产生相关。用抗CD 4单克隆抗体或抗CD 8单克隆抗体体内治疗RF增强的关节炎小鼠，可抑制这些小鼠关节炎的诱导和进展。RF给药严重联合免疫缺陷（SCID）小鼠与关节炎的脾细胞从CII免疫小鼠的转移，延长关节炎和增强的严重程度。这种小鼠模型的RF增强关节炎可能提供了一个有用的工具，用于分析RF阳性患者类风湿性关节炎的发病机制。
In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.