Schröder D, Hehmke B, Klöting I, Schmidt S
Department of Experimental Diabetes Research, Institute of Diabetes Gerhardt Katsch, Karlsburg, Germany.
Diabetes Res. 1991 Jun;17(2):81-91.
Sera from diabetes-prone BB/OK rats were tested for humoral-mediated cytotoxicity to rat pancreatic islet cells, spleen lymphocytes and exocrine pancreatic cells using 51Cr-release assay systems. At the age of 20, 30 and 40 days all cross-sectionally studied BB/OK rats showed cytotoxicity to islet cells but only 37.5%, 25.0% and 63.3% of them exhibited anti-lymphocyte cytotoxicity, respectively. Neither the time course of cytotoxicity to islet cells nor to lymphocytes differed in BB/OK rats developing diabetes compared to animals maintaining normoglycaemia as evidenced in a follow-up study. The decrease of cytotoxicity to islet cells in vitro as observed in the time course study seems to be due to the appearance of an inhibitor of anti-islet cell cytotoxicity in serum from BB/OK rats older than 70 days. However, under conditions avoiding the influence of inhibitory components the observed time course of anti-islet cell cytotoxicity also did not permit to distinguish potential diabetic BB/OK rats from animals maintaining normoglycaemia. In contrast, long-term normoglycaemic BB/OK rats showed a peak value of cytotoxicity to rat exocrine pancreatic cells between 40 and 50 days of age only whereas animals developing diabetes more frequently displayed cytotoxicity in the prediabetic phase. Inhibitory activity against cytotoxicity to exocrine cells was not likewise detectable in BB/OK rat serum. In conclusion, except of more frequently appearing cytotoxicity to rat exocrine pancreatic cells among the investigated BB/OK rats becoming diabetic the cytotoxicity patterns to islet cells and spleen lymphocytes were not predictive for diabetes onset. Thus, humoral-mediated cytotoxicity seems to appear in BB/OK rats as a sign of immune dysregulation characteristic for this animal model at high risk for diabetes rather than in a manner related to disease manifestation.
使用51Cr释放测定系统，检测糖尿病易感BB/OK大鼠的血清对大鼠胰岛细胞、脾淋巴细胞和胰腺外分泌细胞的体液介导细胞毒性。在20、30和40日龄时，所有进行横断面研究的BB/OK大鼠均表现出对胰岛细胞的细胞毒性，但其中分别只有37.5%、25.0%和63.3%表现出抗淋巴细胞细胞毒性。后续研究表明，与维持正常血糖的动物相比，发生糖尿病的BB/OK大鼠对胰岛细胞和淋巴细胞的细胞毒性时间进程并无差异。在时间进程研究中观察到的体外对胰岛细胞细胞毒性的降低，似乎是由于70日龄以上BB/OK大鼠血清中出现了抗胰岛细胞细胞毒性抑制剂。然而，在避免抑制成分影响的条件下，观察到的抗胰岛细胞细胞毒性时间进程也无法区分潜在的糖尿病BB/OK大鼠和维持正常血糖的动物。相比之下，长期血糖正常的BB/OK大鼠仅在40至50日龄时对大鼠胰腺外分泌细胞表现出细胞毒性峰值，而发生糖尿病的动物在糖尿病前期更频繁地表现出细胞毒性。在BB/OK大鼠血清中同样未检测到对外分泌细胞细胞毒性的抑制活性。总之，在所研究的发生糖尿病的BB/OK大鼠中，除了对大鼠胰腺外分泌细胞的细胞毒性更频繁出现外，对胰岛细胞和脾淋巴细胞的细胞毒性模式并不能预测糖尿病的发病。因此，体液介导的细胞毒性似乎在BB/OK大鼠中表现为这种糖尿病高风险动物模型免疫失调的标志，而不是与疾病表现相关的方式。
