Thliveris J A, HayGlass K T, Manchur D, Rector E, Begleiter A, Johnston J B
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.
Histol Histopathol. 2000 Jan;15(1):21-7. doi: 10.14670/HH-15.21.
Insulin-dependent diabetes mellitus (IDDM) is caused by autoimmune destruction of pancreatic beta cells with the primary mechanism being cell mediated. The BB rat develops insulitis and IDDM with many features analogous to the disease in man. In previous studies we reported that weekly administration of 2'-deoxycoformycin (dCF) for four months reduces significantly the incidence of IDDM in the BB rat by 70%, and that the animals remain free of diabetes for a minimum of two months after drug withdrawal. Since the diabetes-prone BB rat is lymphopenic, with a reduction of both CD4 and CD8 cells, the continuous failure of dCF treated animals to develop diabetes may have been due to generalized immunosuppression. To test this possibility, the ability of dCF treated diabetes-free BB rats to mount an immune response after challenge with Ovalbumin was examined five months after drug withdrawal. The results showed that the post-immunization levels of total IgG and specific IgG in these animals did not differ from those observed in non-dCF treated controls nor those of control diabetes-resistant non-lymphopenic BB rats. Moreover, FACS analysis indicated no change in the percentages of total numbers of CD4+ or CD8+ cells between the two groups of animals. Histological assessment of the pancreata of the post-dCF treated animals showed varying degrees of mononuclear cell infiltrates in the islets. These data demonstrate that treatment by dCF is not permanent, and may require intermittent or continuous administration to prevent development of diabetes. Further studies are needed to determine the mechanism of action of dCF in this model of IDDM.
胰岛素依赖型糖尿病（IDDM）是由胰腺β细胞的自身免疫性破坏引起的，主要机制是细胞介导的。BB大鼠会发生胰岛炎和IDDM，其许多特征与人类疾病相似。在先前的研究中，我们报告称，每周给予2'-脱氧助间型霉素（dCF），持续四个月，可使BB大鼠IDDM的发病率显著降低70%，并且在停药后，这些动物至少两个月内不会患糖尿病。由于易患糖尿病的BB大鼠淋巴细胞减少，CD4和CD8细胞均减少，dCF治疗的动物持续不患糖尿病可能是由于全身性免疫抑制。为了验证这种可能性，在停药五个月后，检测了用dCF治疗的无糖尿病BB大鼠在受到卵清蛋白攻击后产生免疫反应的能力。结果表明，这些动物免疫后的总IgG和特异性IgG水平与未用dCF治疗的对照组以及抗糖尿病、非淋巴细胞减少的对照BB大鼠的水平没有差异。此外，流式细胞术分析表明，两组动物之间CD4+或CD8+细胞总数的百分比没有变化。对dCF治疗后动物胰腺的组织学评估显示，胰岛中有不同程度的单核细胞浸润。这些数据表明，dCF的治疗效果不是永久性的，可能需要间歇性或持续性给药以预防糖尿病的发生。需要进一步研究以确定dCF在该IDDM模型中的作用机制。
