Bresnihan B, Jasin H E
J Clin Invest. 1977 Jan;59(1):106-16. doi: 10.1172/JCI108607.
Normal peripheral blood mononuclear cells demonstrated increased DNA synthesis and secretion of newly synthesized protein when suboptimal concentrations of Concanavalin A (Con A) were added to the cultures after 24-h incubation in vitro. Cells stimulated by Con A, 1 mug/ml, after 24-h incubation demonstrated 3.0 times more tritiated thymidine incorporation, and 4.4 times more 14C-amino acid incorporation into newly synthesized secreted protein, than cells stimulated at 0 h (P less than 0.001). The acquisition of increased responsiveness was not abrogated by washing and resuspending the cells in fresh medium. Since the increased responsiveness could be inhibited by the addition to the cultures of small numbers of cells previously activated by Con A it is suggested that the enhanced reactivity acquired in culture represents the loss of a subpopulation of suppressor cells that modulate the T-lymphocyte response. Cells from nine patients with active, untreated systemic lupus erythematosus demonstrated normal responses to optimal concentrations of Con A added at 0 h, but an impaired response to Con A, 1 mug/ml. When these cells were incubated for 24 h, a significant increased response to Con A was not observed. This observation suggests that patients with active SLE lack circulating suppressor cells. When seven SLE patients were again studied after corticosteroid therapy had led to clinical improvement, the response to Con A, 1 mug/ml, added after 24-h incubation was similar to that observed in normal controls, suggesting that suppressor function in SLE returns as disease activity declines.
正常外周血单个核细胞在体外培养24小时后,添加次优浓度的刀豆蛋白A(Con A)时,其DNA合成增加,新合成蛋白质的分泌也增加。在体外培养24小时后,用1微克/毫升Con A刺激的细胞,其氚标记胸腺嘧啶核苷掺入量比在0小时刺激的细胞多3.0倍,14C-氨基酸掺入新合成分泌蛋白中的量比0小时刺激的细胞多4.4倍(P小于0.001)。通过洗涤并将细胞重悬于新鲜培养基中,并未消除这种反应性增加的现象。由于向培养物中添加少量先前被Con A激活的细胞可抑制反应性增加,因此提示在培养中获得的反应性增强代表调节T淋巴细胞反应的抑制细胞亚群的丧失。来自9例未经治疗的活动性系统性红斑狼疮患者的细胞,对0小时添加的最佳浓度Con A表现出正常反应,但对1微克/毫升Con A的反应受损。当这些细胞培养24小时时,未观察到对Con A的反应显著增加。这一观察结果提示活动性SLE患者缺乏循环抑制细胞。当7例SLE患者在皮质类固醇治疗导致临床改善后再次接受研究时,培养24小时后添加1微克/毫升Con A的反应与正常对照中观察到的反应相似,提示随着疾病活动度下降,SLE中的抑制功能恢复。