Smerdon R A, Peakman M, Hussain M J, Vergani D
Department of Immunology, King's College School of Medicine and Dentistry, London, U.K.
Immunology. 1993 Nov;80(3):498-501.
The aim of this study was to investigate whether lymphocyte vaccination can prevent diabetes occurring in the non-obese diabetic (NOD) mouse, an animal model of human insulin-dependent diabetes mellitus (IDDM). The lymphocyte vaccine was composed of lymphocytes isolated from the spleens of diabetic NOD mice, activated in vitro using concanavalin A (Con A) and rendered immunogenic using glutaraldehyde treatment. These cells were used to vaccinate mice at 6 weeks with boosters at weeks 10, 14 and 18. The animals were then monitored for signs of diabetes until week 30. Twenty-eight NOD mice (11 male, 17 female) were T-lymphocyte vaccinated while 35 littermates (14 male, 21 female) were sham vaccinated with the vaccine carrier, as control mice. The percentage of mice remaining non-diabetic was 50% in the T-lymphocyte-vaccinated group compared with 20% in control mice (P < 0.05). When the results were divided according to sex of the mouse the percentage of female NOD mice remaining non-diabetic was 47.1% in the T-lymphocyte-vaccinated group compared to only 9.4% in the controls (P < 0.01), while in the males there was no significant difference between the groups. These results suggest that T-lymphocyte vaccination can prevent diabetes in NOD mice and that it has its greatest effect in females. The therapy is apparently safe and its efficacy indicates that it may be of value in prediabetes in man.
本研究的目的是调查淋巴细胞疫苗接种能否预防非肥胖型糖尿病(NOD)小鼠(一种人类胰岛素依赖型糖尿病(IDDM)的动物模型)发生糖尿病。淋巴细胞疫苗由从糖尿病NOD小鼠脾脏中分离出的淋巴细胞组成,在体外使用刀豆蛋白A(Con A)激活,并经戊二醛处理使其具有免疫原性。这些细胞在6周龄时用于给小鼠接种疫苗,并在第10、14和18周进行加强接种。然后对这些动物进行糖尿病症状监测,直至第30周。28只NOD小鼠(11只雄性,17只雌性)接受了T淋巴细胞疫苗接种,而35只同窝小鼠(14只雄性,21只雌性)作为对照小鼠接受了疫苗载体的假接种。T淋巴细胞疫苗接种组中仍未患糖尿病的小鼠百分比为50%,而对照小鼠为20%(P<0.05)。当根据小鼠性别划分结果时,T淋巴细胞疫苗接种组中仍未患糖尿病的雌性NOD小鼠百分比为47.1%,而对照组仅为9.4%(P<0.01),而在雄性小鼠中,两组之间没有显著差异。这些结果表明,T淋巴细胞疫苗接种可以预防NOD小鼠患糖尿病,并且对雌性小鼠的效果最为显著。该疗法显然是安全的,其疗效表明它可能对人类糖尿病前期具有价值。