Sizemore R C, Dienglewicz R L, Pecunia E, Gottlieb A A
Imreg, Inc., New Orleans, Louisiana 70112.
Clin Immunol Immunopathol. 1991 Aug;60(2):310-8. doi: 10.1016/0090-1229(91)90074-k.
We have developed a system in which human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A (Con A) can be examined for regulatory cell activity upon coculture with responder cells undergoing mitogenic proliferation. Low concentrations of Con A resulted in the induction of helper function, while higher concentrations of Con A induced suppressor activity in the PBMC population. However, for each individual donor a particular concentration of Con A can be found at which point no regulatory cell activity is observed. This "balance point" provides a set of conditions under which the ability of an immunomodulator to up-regulate or down-regulate the system can be studied. The ability of leu-enkephalin to positively or negatively regulate an immune response was examined under these circumstances. The addition of leu-enkephalin to cultures stimulated by Con A at this balance point enhanced both suppressor cell (Ts) and helper cell (Th) activity in a concentration-dependent manner. The induction of Ts activity displayed a bimodal response at concentrations between 10(-12) to 10(-13) M and 10(-9) to 10(-10) M, while the induction of Th activity was consistently observed at 10(-11) M. Similar effects were seen with either of the peptides Tyr-Gly and Tyr-Gly-Gly, corresponding to the first two and three amino acids of the N-terminal ends of the enkephalins. Th activity was consistently enhanced at 10(-13) M Tyr-Gly-Gly and 10(-14) M Tyr-Gly. This suggests that leu-enkephalin may either positively or negatively regulate immune responses and that the intact leu-enkephalin molecule is not required for these effects.
我们开发了一种系统，在该系统中，用伴刀豆球蛋白A（Con A）刺激的人外周血单个核细胞（PBMC）在与经历有丝分裂增殖的反应细胞共培养时，可以检测其调节细胞活性。低浓度的Con A导致辅助功能的诱导，而高浓度的Con A则在PBMC群体中诱导抑制活性。然而，对于每个个体供体，可以找到一个特定浓度的Con A，此时未观察到调节细胞活性。这个“平衡点”提供了一组条件，在这些条件下可以研究免疫调节剂上调或下调该系统的能力。在这些情况下，研究了亮脑啡肽对免疫反应进行正向或负向调节的能力。在这个平衡点向Con A刺激的培养物中添加亮脑啡肽，以浓度依赖的方式增强了抑制细胞（Ts）和辅助细胞（Th）的活性。Ts活性的诱导在10^(-12)至10^(-13) M和10^(-9)至10^(-10) M的浓度之间表现出双峰反应，而Th活性的诱导在10^(-11) M时始终观察到。与脑啡肽N末端的前两个和三个氨基酸相对应的肽Tyr-Gly和Tyr-Gly-Gly中的任何一个都观察到了类似的效果。在10^(-13) M的Tyr-Gly-Gly和10^(-14) M的Tyr-Gly时，Th活性始终增强。这表明亮脑啡肽可能对免疫反应进行正向或负向调节，并且这些作用不需要完整的亮脑啡肽分子。
