Hayward A R, Shriber M, Cooke A, Waldmann H
Dept of Pediatrics, University of Colorado School of Medicine, Denver 80262.
J Autoimmun. 1993 Jun;6(3):301-10. doi: 10.1006/jaut.1993.1026.
Non-obese diabetic (NOD) mice were injected with a rat monoclonal antibody to CD4 from birth every two weeks through 6 months of age. These animals gained weight normally but < 11% of their spleen T cells were CD4+, compared with 28% of CD4+ in controls injected with polyclonal rat IgG. The reduction in CD4 cell percentage was associated with a reduction in the number of cells in the thymus and spleen following the injection. CD4+ cells which survived the injections were nevertheless able to enter cell cycle when stimulated by Con A. None of the CD4-treated NOD mice became diabetic by 6 months of age and none of the animals studied histologically at this time had insulitis. At 9 months of age (three months after stopping the CD4 injections) the mice made antibody to human IgG. At 1 year of age most of the male mice had insulitis, although none of the male or female mice had become spontaneously diabetic. Two thirds of animals injected with cyclophosphamide at 16 months became diabetic within 3 weeks. The results confirm that treatment with CD4 antibody in the first 6 months suffices to reduce the incidence of diabetes in NOD mice. The treatment does not prevent the subsequent development of insulitis in injected mice and does not prevent the accumulation of cells capable of causing overt diabetes after cyclophosphamide injection.
从出生起，每两周给非肥胖型糖尿病（NOD）小鼠注射一次抗CD4大鼠单克隆抗体，直至6月龄。这些动物体重正常增加，但脾脏T细胞中CD4⁺细胞的比例不到11%，而注射多克隆大鼠IgG的对照组中CD4⁺细胞比例为28%。CD4细胞百分比的降低与注射后胸腺和脾脏中的细胞数量减少有关。经注射后存活的CD4⁺细胞在受到刀豆蛋白A刺激时仍能进入细胞周期。6月龄时，接受CD4治疗的NOD小鼠均未患糖尿病，此时进行组织学研究的动物均无胰岛炎。9月龄时（停止注射CD4后三个月），小鼠产生了抗人IgG抗体。1岁时，大多数雄性小鼠出现胰岛炎，尽管雄性和雌性小鼠均未自发患糖尿病。16月龄时注射环磷酰胺的动物中有三分之二在3周内患糖尿病。结果证实，在最初6个月用CD4抗体治疗足以降低NOD小鼠患糖尿病的发生率。该治疗不能预防注射小鼠随后发生胰岛炎，也不能预防注射环磷酰胺后能够导致明显糖尿病的细胞积累。
