Maruyama T, Watanabe K, Takei I, Kasuga A, Shimada A, Yanagawa T, Kasatani T, Suzuki Y, Kataoka K
Department of Medicine, Social Insurance Saitama Chuo Hospital, Japan.
Diabetes Res. 1991 May;17(1):37-41.
To elucidate the role of natural killer (NK) cells in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse, we examined whether or not cyclophosphamide-induced diabetes occurs in NOD mice intraperitoneally (i.p.) injected with anti-asialo GM1 antibody. Two weeks after a single intraperitoneal injection of cyclophosphamide, none of the 24 NOD mice which had previously been treated with antiasialo GM1 antibody, 2-3 times per week for either 2 or 3 weeks, had developed indications of diabetes such as glycosuria or a high plasma glucose level. On the other hand, signs of diabetes were found in 10 of 24 control NOD mice injected with normal rabbit Ig instead of anti-asialo GM1 antibody (p less than 0.01). The NK cell activities of spleen cells from anti-asialo GM1 antibody-treated mice were significantly lower than those of control mice (p less than 0.01). Flowcytometry analysis demonstrated that anti-asialo GM1 antibody-positive cells had disappeared from the spleens of anti-asialo GM1 antibody-injected mice but no suppression of CD8+ and CD4+ cells could be demonstrated. These observations suggest that NK cells are involved in the development of diabetes in NOD mice.
为阐明自然杀伤（NK）细胞在非肥胖糖尿病（NOD）小鼠糖尿病发病机制中的作用，我们检测了腹腔注射抗去唾液酸GM1抗体的NOD小鼠是否会发生环磷酰胺诱导的糖尿病。在单次腹腔注射环磷酰胺两周后，之前每周接受2 - 3次抗去唾液酸GM1抗体治疗，持续2或3周的24只NOD小鼠中，没有一只出现糖尿病迹象，如糖尿或高血糖水平。另一方面，在注射正常兔Ig而非抗去唾液酸GM1抗体的24只对照NOD小鼠中，有10只出现了糖尿病迹象（p < 0.01）。抗去唾液酸GM1抗体处理小鼠的脾细胞NK细胞活性显著低于对照小鼠（p < 0.01）。流式细胞术分析表明，抗去唾液酸GM1抗体阳性细胞已从注射抗去唾液酸GM1抗体小鼠的脾脏中消失，但未发现对CD8 +和CD4 +细胞的抑制作用。这些观察结果表明，NK细胞参与了NOD小鼠糖尿病的发生发展。
