Mann D R, Ansari A A, Akinbami M A, Wallen K, Gould K G, McClure H M
Morehouse School of Medicine, Emory University School of Medicine, Atlanta, Georgia 30310.
J Clin Endocrinol Metab. 1994 Feb;78(2):292-8. doi: 10.1210/jcem.78.2.8106614.
We examined the effect of treatment with a LH-releasing hormone (LHRH) agonist (Ag), antagonist (Ant), or Ant and androgen (Ant/And) for the first 4 months of postnatal life on lymphocyte subsets and cellular and humorally mediated immune responses in juvenile and adult male monkeys. We also determined the effect of 9 weeks of Ant treatment on lymphocyte subsets in adult male monkeys. Adult male monkeys that had been treated neonatally with an Ag had increased levels of CD8-positive (CD8+) T-cells and reduced levels of B-cells compared to vehicle-treated controls. Lymphocytes from these animals also showed an elevated proliferative response to a variety of mitogens compared to cells from control animals. Antibody production in response to tetanus toxoid was normal in treated animals. Other neonates treated with Ant/And exhibited subnormal levels of lymphocytes, CD8+ T-cells, and B-cells at 4 months of age. Similar changes, but of lesser magnitude, were observed in animals treated with Ant alone. At 6 months of age, lymphocytes from both groups of Ant-treated monkeys exhibited an above normal proliferative response to streptolysin-O, but not to other mitogens. At 18 months of age, animals treated with Ant alone produced more antitetanus antibody in response to a tetanus toxoid booster than the controls or Ant/And-treated animals. Ant treatment was without major effect on lymphocyte subsets in adult monkeys. Serum LH and testosterone levels declined, and there was a small but significant increase in B-cells, lymphocytes expressing the interleukin-2 receptor, and the CD4+/CD8+ T-cell ratio during treatment, but these parameters normalized during the posttreatment period. The data suggest that chronic neonatal treatment with an Ag or Ant alters the development of immune system responses in male primates. The significance of these changes and their impact on the ability of these animals to respond to pathogenic agents is under investigation.
我们研究了在出生后前4个月用促黄体生成素释放激素（LHRH）激动剂（Ag）、拮抗剂（Ant）或拮抗剂与雄激素联合使用（Ant/And）对幼年和成年雄性猴子淋巴细胞亚群以及细胞介导和体液介导免疫反应的影响。我们还确定了9周的Ant治疗对成年雄性猴子淋巴细胞亚群的影响。与用赋形剂处理的对照相比，出生时用Ag处理的成年雄性猴子CD8阳性（CD8 +）T细胞水平升高，B细胞水平降低。与对照动物的细胞相比，这些动物的淋巴细胞对多种有丝分裂原的增殖反应也增强。经处理的动物对破伤风类毒素的抗体产生正常。其他用Ant/And处理的新生动物在4个月大时淋巴细胞、CD8 + T细胞和B细胞水平低于正常。在用Ant单独处理的动物中观察到类似变化，但程度较小。在6个月大时，两组经Ant处理的猴子的淋巴细胞对链球菌溶血素-O表现出高于正常的增殖反应，但对其他有丝分裂原无此反应。在18个月大时，单独用Ant处理的动物对破伤风类毒素加强免疫产生的抗破伤风抗体比对照或用Ant/And处理的动物更多。Ant治疗对成年猴子的淋巴细胞亚群没有重大影响。治疗期间血清促黄体生成素和睾酮水平下降，B细胞、表达白细胞介素-2受体的淋巴细胞以及CD4 + /CD8 + T细胞比率有小幅但显著的增加，但这些参数在治疗后阶段恢复正常。数据表明，出生后长期用Ag或Ant处理会改变雄性灵长类动物免疫系统反应的发育。这些变化的意义及其对这些动物应对病原体能力的影响正在研究中。
