Lotz M, Tsoukas C D, Robinson C A, Dinarello C A, Carson D A, Vaughan J H
J Clin Invest. 1986 Sep;78(3):713-21. doi: 10.1172/JCI112631.
Synovial fluid mononuclear cells (SFMC) from patients with active rheumatoid arthritis characteristically respond poorly to mitogens. In this study, mitogenic antibodies reactive with the CD3(T3) antigen on human T lymphocytes were used to analyze the basis for the deficiency. OKT3-induced proliferation and release of interleukin 1 (IL-1) and interleukin 2 (IL-2) from SFMC were depressed in all patients. Purified IL-1 or recombinant IL-2 restored proliferative responses in SFMC and increased IL-2 receptor density. Exogenous IL-1 also enhanced IL-2 release. Fractionation of SFMC supernatants on phosphocellulose columns revealed the presence of IL-1 and a potent IL-1 inhibitor. The monocyte-derived IL-1 inhibitor blocked IL-1-dependent responses of normal peripheral blood lymphocytes to OKT3, but had no effect on IL-2-dependent events. These results suggest that IL-1 inhibitor(s) in SFMC impair(s) OKT3-induced mitogenesis by interfering with the effects of IL-1 on T lymphocytes. The net result is deficient IL-2 secretion, IL-2 receptor expression, and impaired cellular proliferation. This novel inhibitory circuit provides a rational explanation for the diminished function of synovial fluid T lymphocytes in rheumatoid arthritis patients.
活动性类风湿关节炎患者的滑膜液单核细胞（SFMC）对丝裂原的反应通常较差。在本研究中，使用与人T淋巴细胞上CD3（T3）抗原反应的促有丝分裂抗体来分析这种缺陷的基础。所有患者的SFMC中，OKT3诱导的增殖以及白细胞介素1（IL-1）和白细胞介素2（IL-2）的释放均受到抑制。纯化的IL-1或重组IL-2可恢复SFMC中的增殖反应并增加IL-2受体密度。外源性IL-1也增强了IL-2的释放。在磷酸纤维素柱上对SFMC上清液进行分级分离，发现存在IL-1和一种有效的IL-1抑制剂。单核细胞衍生的IL-1抑制剂可阻断正常外周血淋巴细胞对OKT3的IL-1依赖性反应，但对IL-2依赖性事件无影响。这些结果表明，SFMC中的IL-1抑制剂通过干扰IL-1对T淋巴细胞的作用来损害OKT3诱导的有丝分裂。最终结果是IL-2分泌不足、IL-2受体表达受损以及细胞增殖受损。这种新的抑制回路为类风湿关节炎患者滑膜液T淋巴细胞功能减弱提供了合理的解释。
