Fischer A, Le Deist F, Durandy A, Griscelli C
J Immunol. 1985 Feb;134(2):815-9.
Prostaglandin E2 (PGE2) is a potent inhibitor of immune functions. Two possible mechanisms of PGE2-mediated suppression have been proposed: one is a direct inhibitory effect exerted on interleukin 2-producing T cells; the second is mediated by the activation of nonspecific suppressor T lymphocytes. We previously showed that PGE2 can directly activate human T lymphocytes to suppress lymphocyte proliferation and B lymphocyte maturation. Herein is described the binding of 10 to 30% of human peripheral blood T lymphocytes to insolubilized PGE2 coated to albumin-Sepharose. The T lymphocytes that bound PGE2 (PGE2(+] could be eluted by the addition of serum and gentle shaking of the beads. The following data indicated the specificity of the binding: i) T lymphocytes after an overnight incubation, a condition known to abolish sensitivity to PGE2, lost their affinity for PGE2; ii) preincubation of T lymphocytes with PGE2 blocked the binding; iii) PGE2(+) T cells bound PGE after a 24-hr incubation, whereas PGE2(-) T cells did not. Few T cells bound albumin, and only a small percentage (7 to 9%) bound 6-keto-prostaglandin F1 alpha-coated beads. Among PGE2(+) T cells, there was a slight increase in the percentage of OKT8+ cells. Although T cells that had no affinity for PGE2 (PGE2(-] proliferated as well as unseparated T lymphocytes when stimulated with mitogens or antigens, the proliferative response of the PGE2(+) subset was poor. Moreover, PGE2(+) T lymphocytes did exert a strong suppressor activity on mitogen- or allogeneic cell-induced lymphocyte proliferation as well as on pokeweed mitogen-driven B cell maturation into Ig-containing cells. PGE2(-) T lymphocytes were shown not to exert a significant suppressor activity in these assays. The PGE2(+) subset-mediated suppression was not secondary to a carry-over of PGE2 released from the beads, because its suppressor activity was not altered by the addition of an anti-PGE2 serum. Moreover, PGE2(-) T lymphocytes were not sensitive to the inhibitory activity on cell proliferation of PGE2. These results indicate that a given functional subset of peripheral blood T lymphocytes binds PGE2, and that at least some of them are activated into suppressor T cells. The relationship between the PGE2-activatable T suppressor subset and other functionally defined suppressor T cells remains to be clarified; it is suggested, however, that PGE2 can act as an immunoregulator through the activation of identifiable suppressor T cells.
前列腺素E2（PGE2）是免疫功能的强效抑制剂。关于PGE2介导的免疫抑制作用，已提出两种可能机制：一种是对产生白细胞介素2的T细胞直接产生抑制作用；另一种是由非特异性抑制性T淋巴细胞的激活介导。我们之前发现PGE2可直接激活人T淋巴细胞，从而抑制淋巴细胞增殖和B淋巴细胞成熟。本文描述了10%至30%的人外周血T淋巴细胞与包被在白蛋白-琼脂糖凝胶上的不溶性PGE2的结合情况。结合了PGE2的T淋巴细胞（PGE2(+)）可通过加入血清并轻轻摇晃珠子而被洗脱。以下数据表明了这种结合的特异性：i）过夜孵育后的T淋巴细胞，这种情况已知会消除对PGE2的敏感性，失去了对PGE2的亲和力；ii）T淋巴细胞与PGE2预孵育会阻断这种结合；iii）PGE2(+) T细胞在孵育24小时后仍能结合PGE，而PGE2(-) T细胞则不能。很少有T细胞结合白蛋白，只有一小部分（7%至9%）结合包被有6-酮-前列腺素F1α的珠子。在PGE2(+) T细胞中，OKT8+细胞的百分比略有增加。虽然对PGE2没有亲和力的T细胞（PGE2(-)）在用有丝分裂原或抗原刺激时与未分离的T淋巴细胞增殖情况相同，但PGE2(+)亚群的增殖反应较差。此外，PGE2(+) T淋巴细胞对有丝分裂原或同种异体细胞诱导的淋巴细胞增殖以及对商陆有丝分裂原驱动的B细胞成熟为含Ig细胞均具有强烈的抑制活性。在这些实验中，PGE2(-) T淋巴细胞未表现出明显的抑制活性。PGE2(+)亚群介导的抑制作用并非继发于珠子释放的PGE2的残留，因为加入抗PGE2血清后其抑制活性并未改变。此外，PGE2(-) T淋巴细胞对PGE2对细胞增殖的抑制活性不敏感。这些结果表明，外周血T淋巴细胞的特定功能亚群可结合PGE2，并且其中至少一些被激活成为抑制性T细胞。PGE2可激活的抑制性T细胞亚群与其他功能定义的抑制性T细胞之间的关系仍有待阐明；然而，提示PGE2可通过激活可识别的抑制性T细胞而作为一种免疫调节剂发挥作用。
