Herold K C, Baumann E, Vezys V, Buckingham F
Department of Medicine, University of Illinois at Chicago 60612, USA.
J Autoimmun. 1997 Feb;10(1):17-25. doi: 10.1006/jaut.1996.0108.
Insulin dependent diabetes mellitus (IDDM) is likely to be due to the immunologic destruction of the islets of Langerhans. However, the relative importance of expression of a unique set of islet antigens or of differences in immune responses to those antigens in determining susceptibility to auto-immune diabetes is unknown. To a large extent, the reason for this uncertainty is the difficulty in directly identifying islet antigens expressed in vivo. We have studied the relationship between islet antigen expression, immune responsiveness to islet antigens, and the development of diabetes in diabetes induced by multiple low-doses of streptozotocin (STZ) in mice of the H-2d haplotype. We identified the expression of relevant islet antigens by testing the ability of STZ treated islets to induce tolerance to diabetes in C57BL/KsJ mice after intrathymic transplantation. C57BL/KsJ but not BALB/cByJ mice developed hyperglycaemia and insulitis following STZ treatment. Interferon-gamma transcription was detected in intrapancreatic lymphocytes from C57BL/KsJ mice but at lower levels in cell from BALB/cByJ. IL-4 levels were higher in BALB/cByJ than C57BL/KsJ. Intrathymic STZ-treated islets from syngeneic mice induced tolerance to diabetes in C57BL/KsJ mice following transient depletion of mature peripheral T cells, but islets from resistant BALB/cByJ mice did not induce tolerance to disease in C57BL/KsJ mice even though they did cause tolerance to the alloantigens. (C57BL/KsJ x BALB/cByJ)F1 mice developed hyperglycaemia like the susceptible parent following STZ treatment, and islets from these mice induced tolerance to MDSDM when treated with STZ and transplanted intrathymically into C57BL/KsJ. We conclude the expression of islet antigens and the intrapancreatic responses to STZ treated islets differs between mice that are susceptible and resistant to multi-dose streptozotocin induced diabetes mellitus.
胰岛素依赖型糖尿病（IDDM）可能是由于朗格汉斯胰岛的免疫性破坏所致。然而，一组独特的胰岛抗原的表达或对这些抗原的免疫反应差异在决定自身免疫性糖尿病易感性方面的相对重要性尚不清楚。在很大程度上，这种不确定性的原因在于难以直接鉴定体内表达的胰岛抗原。我们研究了H-2d单倍型小鼠中胰岛抗原表达、对胰岛抗原的免疫反应性与多次低剂量链脲佐菌素（STZ）诱导的糖尿病发展之间的关系。我们通过检测经STZ处理的胰岛在胸腺内移植后诱导C57BL/KsJ小鼠对糖尿病产生耐受性的能力，来鉴定相关胰岛抗原的表达。STZ处理后，C57BL/KsJ小鼠而非BALB/cByJ小鼠出现高血糖和胰岛炎。在C57BL/KsJ小鼠的胰腺内淋巴细胞中检测到γ干扰素转录，但在BALB/cByJ小鼠的细胞中水平较低。BALB/cByJ小鼠的IL-4水平高于C57BL/KsJ小鼠。同基因小鼠经胸腺内STZ处理的胰岛在成熟外周T细胞短暂耗竭后，可诱导C57BL/KsJ小鼠对糖尿病产生耐受性，但抗性BALB/cByJ小鼠的胰岛即使能诱导对同种异体抗原的耐受性，也不能诱导C57BL/KsJ小鼠对疾病产生耐受性。（C57BL/KsJ×BALB/cByJ）F1小鼠在STZ处理后像易感亲本一样出现高血糖，这些小鼠的胰岛在用STZ处理并胸腺内移植到C57BL/KsJ小鼠后，可诱导对多剂量链脲佐菌素诱导的糖尿病（MDSDM）产生耐受性。我们得出结论，对多剂量链脲佐菌素诱导的糖尿病易感和抗性小鼠之间，胰岛抗原的表达以及胰腺内对经STZ处理的胰岛的反应存在差异。
