Chang M P, Yamaguchi D T, Yeh M, Taylor A N, Norman D C
Education and Clinic Center (GRECC), Veteran Administration Medical Center, West Los Angeles, CA.
Int J Immunopharmacol. 1994 Apr;16(4):345-57. doi: 10.1016/0192-0561(94)90010-8.
Although attempts have been made to assess the effect of ethanol on the immune responses in individuals with fetal alcohol syndrome, there is no consensus as to the effect of ethanol on the immune system. Evidence that fetal alcohol-exposed (FAE) humans and animals have diminished proliferative response of T-cells to mitogenic lectins is well established. However, little is known about the mechanism of a toxic effect of ethanol on T-cell growth. Thus, a rat model was used to delineate the mode of ethanol action on T-cell proliferation. We found that the diminished T-cell proliferation in young adult FAE rats was due to a decreased responsiveness to interleukin 2 (IL2), but not to an impaired production of IL2 and expression of IL2 receptors (IL2R). Furthermore, the decreased proliferative response did not result from the presence of an excessive suppressor T-cell activity. Measurements of [Ca+2]i and T-cell proliferation were concurrently performed in batches of cells from the same animals. It was demonstrated that an increase in [Ca+2]i induced by Concanavalin A (Con A) in T-cells from FAE rats was not impaired, although the T-cell proliferation induced by Con A was significantly diminished. The results of the IL2-binding study showed that the Kd values and the number of both high- and low-affinity IL2R binding sites on the T-cells of FAE rats were comparable to those of pair-, or chow-fed rats. Finally, the results of the kinetics and rate of the internalization of IL2 showed that (1) the amount of the internalized IL2 was significantly reduced in T-cells from FAE rats, and (2) the half-time (t1/2) for dissociation of IL2 from the receptors in the T-cells from FAE rats was also greater than that of the control rats. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2-IL2R interaction.
尽管已经有人尝试评估乙醇对患有胎儿酒精综合征个体免疫反应的影响，但对于乙醇对免疫系统的影响尚无定论。有充分证据表明，暴露于乙醇的胎儿（FAE）的人类和动物的T细胞对有丝分裂原凝集素的增殖反应减弱。然而，关于乙醇对T细胞生长产生毒性作用的机制却知之甚少。因此，使用大鼠模型来阐明乙醇对T细胞增殖的作用方式。我们发现，年轻成年FAE大鼠的T细胞增殖减少是由于对白细胞介素2（IL2）的反应性降低，而非IL2产生受损和IL2受体（IL2R）表达受损。此外，增殖反应降低并非由过度的抑制性T细胞活性所致。对来自同一动物的细胞批次同时进行[Ca+2]i和T细胞增殖的测量。结果表明，刀豆球蛋白A（Con A）诱导的FAE大鼠T细胞中[Ca+2]i增加并未受损，尽管Con A诱导的T细胞增殖显著减少。IL2结合研究结果表明，FAE大鼠T细胞上高亲和力和低亲和力IL2R结合位点的Kd值及数量与配对或正常饮食喂养大鼠的相当。最后，IL2内化动力学和速率的结果表明：（1）FAE大鼠T细胞中内化的IL2量显著减少；（2）FAE大鼠T细胞中IL2从受体解离的半衰期（t1/2）也长于对照大鼠。综合这些结果表明，乙醇通过干扰IL2 - IL2R相互作用后的事件来抑制T细胞增殖。
