Diaz-Sanchez D, Lee T H, Kemeny D M
Department of Allergy and Allied Respiratory Disorders, United Medical School of Guy's Hospital, London.
Immunology. 1993 Feb;78(2):226-36.
Ricin, a toxic lectin from castor beans greatly enhances IgE responses to bee venom phospholipase A2 (PLA2) in high and low IgE responder strains of rat. The increase in IgE is accompanied by a 60% reduction in the number of CD8+ but not CD4+ T cells in the spleen. Optimal enhancement of IgE by ricin occurs when it is given at the same time as the antigen or 24 hr later, suggesting that it acts on cells which were activated as a consequence of immunization. Radio ligand-binding studies with 125I ricin were used to compare the number of ricin binding sites on CD4+ and CD8+ T cells. No difference was seen in either the affinity or the number of receptors for ricin on the CD4+ and CD8+ T cells of unimmunized rats. In contrast, CD8+ T cells taken from rats which had been immunized with 10 micrograms of PLA2 24 hr earlier demonstrated considerably more ricin receptors (3.9 x 10(7) +/- 2.2 x 10(6) binding sites/cell) than CD4+ T cells (3.19 x 10(6) +/- 1.08 x 10(6) binding sites/cell). However the affinity of the receptors for ricin was unchanged. Cytofluorographic analysis with fluorescein isothiocyanate (FITC)-labelled ricin confirmed these observations and indicated that increased ricin binding occurred on a subpopulation of CD8+ T cells. The effect of CD8+ T cells on IgE regulation was investigated by adoptive transfer. 1 x 10(8) highly purified (> 98%) splenic CD8+ T cells collected from Brown Norway rats 3 days after immunization with 10 micrograms of PLA2 were adoptively transferred to naive, syngeneic recipients. The IgE antibody response to PLA2 + A1(OH)3 seen in these animals was reduced by 91%. Adoptive transfer of CD4+ T cells from the same donor animals did not induce suppression and nor did adoptive transfer of CD8+ T cells from animals given both ricin and PLA2. However, when recipients of CD8+ T cells taken from rats immunized with PLA2 were immunized with a different antigen [ovalbumin (OVA)] and A1(OH)3 the IgE antibody response was also suppressed, although to a lesser extent (66%). These results show that co-administration of ricin and PLA2 depletes a subpopulation of ricin-sensitive, early activated CD8+ T cells and that these CD8+ T cells are potent suppressors of the primary IgE response.
蓖麻毒素是一种来自蓖麻子的毒性凝集素，它能显著增强大鼠高、低IgE反应品系对蜂毒磷脂酶A2（PLA2）的IgE反应。IgE的增加伴随着脾脏中CD8⁺ 而非CD4⁺ T细胞数量减少60%。当蓖麻毒素与抗原同时给予或在24小时后给予时，对IgE的增强作用最佳，这表明它作用于因免疫而被激活的细胞。用¹²⁵I标记的蓖麻毒素进行放射性配体结合研究，以比较CD4⁺ 和CD8⁺ T细胞上蓖麻毒素结合位点的数量。在未免疫大鼠的CD4⁺ 和CD8⁺ T细胞上，蓖麻毒素的亲和力或受体数量均未观察到差异。相比之下，从24小时前用10微克PLA2免疫的大鼠中获取的CD8⁺ T细胞显示出比CD4⁺ T细胞（3.19×10⁶ ± 1.08×10⁶ 结合位点/细胞）多得多的蓖麻毒素受体（3.9×10⁷ ± 2.2×10⁶ 结合位点/细胞）。然而，受体对蓖麻毒素的亲和力没有变化。用异硫氰酸荧光素（FITC）标记的蓖麻毒素进行细胞荧光分析证实了这些观察结果，并表明蓖麻毒素结合增加发生在CD8⁺ T细胞的一个亚群上。通过过继转移研究了CD8⁺ T细胞对IgE调节的作用。从用10微克PLA2免疫3天后的棕色挪威大鼠中收集1×10⁸ 高度纯化（>98%）的脾CD8⁺ T细胞，过继转移给同基因的未免疫受体。这些动物中对PLA2 + A1(OH)₃ 的IgE抗体反应降低了91%。来自相同供体动物的CD4⁺ T细胞过继转移未诱导抑制作用，同时给予蓖麻毒素和PLA2的动物的CD8⁺ T细胞过继转移也未诱导抑制作用。然而，当用PLA2免疫的大鼠的CD8⁺ T细胞受体用不同抗原[卵清蛋白（OVA）]和A1(OH)₃ 免疫时，IgE抗体反应也受到抑制，尽管程度较小（66%）。这些结果表明，蓖麻毒素和PLA2共同给药会耗尽蓖麻毒素敏感的早期激活CD8⁺ T细胞亚群，并且这些CD8⁺ T细胞是原发性IgE反应的有效抑制因子。
