Neubert R, Helge H, Neubert D
University Medical Center, Free University Berlin.
Life Sci. 1995;56(6):437-44. doi: 10.1016/0024-3205(94)00908-2.
Marmosets (Callithrix jacchus) were vaccinated with tetanus toxoid and boostered 3 months and 1 year following the initial immunization. During this period, the proliferative response of lymphocytes (3H-thymidine incorporation) to the recall antigen was measured in vitro in blood samples 7 times. The experimental procedure proved to be suitable to monitor a defined but complex function of the immune system, and to assess possible substance-induced alterations with minimal stress or discomfort for the non-human primates. As a first example, a possible interference by a single very small dose (100 ng/kg body weight) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given at the time of the second booster was evaluated. No reduction in the in vitro response of the lymphocytes to recall antigen was observed under the experimental conditions used, and the extent of the 3H-thymidine incorporation was not significantly different in the groups. When the ratio of the responses between the first and the second booster was taken as a measure, there was a slight but statistically significant increase in this ratio for the lymphocytes of the TCDD-treated marmosets over that of reference animals. The limitations of these attempts to develop a test system and evaluate a substance-induced effect, and possible improvements of the test, e.g. with multivaccination, are discussed. It is suggested to use this approach also after routine multivaccination in children to assess possible substance-induced effects on immunological variables. This would allow an excellent comparison of experimental and clinical data obtained in primates with an identical technology.
用破伤风类毒素对狨猴(绢毛猴)进行免疫接种,并在初次免疫后3个月和1年进行加强免疫。在此期间,7次体外检测血液样本中淋巴细胞对回忆抗原的增殖反应(3H-胸腺嘧啶核苷掺入)。实验程序被证明适用于监测免疫系统的一种特定但复杂的功能,并以对非人灵长类动物最小的压力或不适来评估可能的物质诱导的改变。作为第一个例子,评估了在第二次加强免疫时给予单次非常小剂量(100 ng/kg体重)的2,3,7,8-四氯二苯并对二恶英(TCDD)可能产生的干扰。在所使用的实验条件下,未观察到淋巴细胞对回忆抗原的体外反应降低,且各组中3H-胸腺嘧啶核苷掺入的程度无显著差异。当以第一次和第二次加强免疫之间的反应比率作为衡量标准时,TCDD处理的狨猴淋巴细胞的该比率相对于对照动物略有但具有统计学意义的增加。讨论了开发测试系统和评估物质诱导效应这些尝试的局限性,以及测试可能的改进方法,例如多次接种。建议在儿童进行常规多次接种后也采用这种方法来评估可能的物质诱导对免疫变量的影响。这将能够对用相同技术在灵长类动物中获得的实验数据和临床数据进行出色的比较。