Alarcon-Segovia D, Ruiz-Arguelles A, Llorente L
J Immunol. 1979 May;122(5):1855-62.
We have previously shown that an anti-ribonucleoprotein (RNP) IgG can penetrate into live human mononuclear cells (MNC) having receptors for the Fc portion of IgG. Because T cells with such receptors (Tgamma cells) seem to behave as suppressor cells in immune regulation and because this suppressor function is diminished in diseases where antinuclear antibodies appear, we considered the possibility that antinuclear IgG antibody could penetrate Tgamma cells and affect them. Herein we show that fluorescein-labeled anti-RNP IgG can penetrate into Tgamma cells, enriched by either mitogenic stimulation or separation with a subpopulation of T cells with low affinity for sheep erythrocytes. Incubation of MNC with anti-RNP IgG before carrying out the separation procedures resulted in apparent loss of Tgamma cells at the end of separation. To confirm that deletion had actually occurred, we performed a cytotoxicity assay using 51Cr-labeled T cells. Anti-RNP IgG had a significantly higher cytotoxic effect that normal IgG on T cells, particularly on those with low affinity for sheep erythrocytes that include most Tgamma cells. Suppressor cell function studied in a system where it was expanded, by either 7-day culture or incubation with concanavalin A, and detected in a reverse plaque-forming cell assay with rabbit anti-human immunoglobulin-developing antibody was found to be abrogated by the addition of anti-RNP IgG to the suppressor function-expanding cultures. Controls in Ig-free medium, or medium supplemented with normal human IgG, aggregated normal human IgG, BSA-anti-BSA immune complexes, or F(ab')2 fragments of the anti-RNP IgG, did not abrogate suppressor cell function. This indicates that the abrogation of suppressor cell function by anti-RNP IgG is due to its penetration into Tgamma cells. Suppressor cell loss and/or dysfunction caused by penetration of antinuclear antibodies into Tgamma cells may lead to the self-perpetuation of autoimmune disease.
我们之前已经表明，一种抗核糖核蛋白（RNP）IgG能够穿透具有IgG Fc段受体的活的人单核细胞（MNC）。因为具有此类受体的T细胞（Tγ细胞）在免疫调节中似乎起着抑制细胞的作用，且因为这种抑制功能在出现抗核抗体的疾病中会减弱，所以我们考虑抗核IgG抗体可能穿透Tγ细胞并对其产生影响的可能性。在此我们表明，荧光素标记的抗RNP IgG能够穿透Tγ细胞，这些Tγ细胞通过丝裂原刺激或与对绵羊红细胞亲和力低的T细胞亚群分离而得到富集。在进行分离程序之前，用抗RNP IgG孵育MNC，导致分离结束时Tγ细胞明显减少。为了证实确实发生了缺失，我们使用51Cr标记的T细胞进行了细胞毒性试验。抗RNP IgG对T细胞，尤其是对那些对绵羊红细胞亲和力低的T细胞（包括大多数Tγ细胞）的细胞毒性作用明显高于正常IgG。在一个通过7天培养或与刀豆球蛋白A孵育来扩增抑制细胞功能，并在使用兔抗人免疫球蛋白显影抗体的反向空斑形成细胞试验中检测的系统中研究发现，向抑制细胞功能扩增培养物中添加抗RNP IgG会消除抑制细胞功能。在无Ig培养基或补充有正常人IgG、聚集的正常人IgG、BSA - 抗BSA免疫复合物或抗RNP IgG的F(ab')2片段的培养基中的对照，不会消除抑制细胞功能。这表明抗RNP IgG对抑制细胞功能的消除是由于其穿透进入Tγ细胞。抗核抗体穿透Tγ细胞导致的抑制细胞丢失和/或功能障碍可能导致自身免疫性疾病的持续存在。
