Ramiya V K, Shang X Z, Wasserfall C H, Maclaren N K
Department of Pathology and Laboratory Medicine, University of Florida, Gainesville, USA.
Autoimmunity. 1997;26(3):139-51. doi: 10.3109/08916939708994736.
Islet cell antigens have been administered orally and intravenously (I.V.) to NOD mice to assess their abilities to protect from or delay the onset of diabetes, and thereby provide insights that may have therapeutic implications in human trials. Whereas we and others have observed a delay in the onset of diabetes in NOD mice that have been fed with insulin from early life, we report here for the first time that feedings with porcine GAD65 alone (p = 0.226) or in combination with insulin (p = 0.011), have anti-diabetic effects in a prolonged study period (>400 days). While antigen-specific inhibitions of in vitro lymphocytic proliferation responses were seen (p < 0.05), antibody levels were unaffected by oral antigen treatments. IFN-gamma mRNA levels were downregulated in the islet infiltrates following oral antigen treatments while IL-2 and TNF-beta were expressed in all instances. We also observed that I.V. human recombinant GAD65, and porcine GAD given at weaning, delayed diabetes onset (p = 0.004) while similar treatments with a variety of inactive insulin preparations were generally ineffective. These findings thus indicate varying effects of oral and I.V. autoantigen administrations on the development of diabetes in NOD mice, and describe the immunological processes induced by oral autoantigen treatments.
已将胰岛细胞抗原经口和静脉内（I.V.）给予非肥胖糖尿病（NOD）小鼠，以评估它们预防或延缓糖尿病发病的能力，从而提供可能对人体试验具有治疗意义的见解。虽然我们和其他人观察到从幼年开始喂食胰岛素的NOD小鼠糖尿病发病延迟，但我们在此首次报告，在延长的研究期（>400天）内，单独喂食猪GAD65（p = 0.226）或与胰岛素联合喂食（p = 0.011）具有抗糖尿病作用。虽然观察到体外淋巴细胞增殖反应有抗原特异性抑制（p < 0.05），但抗体水平不受口服抗原治疗的影响。口服抗原治疗后，胰岛浸润中的IFN-γ mRNA水平下调，而IL-2和TNF-β在所有情况下均有表达。我们还观察到，静脉内给予人重组GAD65以及断奶时给予猪GAD可延迟糖尿病发病（p = 0.004），而用各种无活性胰岛素制剂进行类似治疗通常无效。因此，这些发现表明口服和静脉内给予自身抗原对NOD小鼠糖尿病发展有不同影响，并描述了口服自身抗原治疗诱导的免疫过程。
