Mucosal antigen primes diabetogenic cytotoxic T-Lymphocytes regardless of dose or delivery route
Mucosal antigen primes diabetogenic cytotoxic T-Lymphocytes regardless of dose or delivery route
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DOI：
10.2337/diabetes.50.4.771
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发表时间：
2001-04-01
期刊：
影响因子：
7.7
通讯作者：
Harrison, LC
中科院分区：
文献类型：
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作者：
Hänninen, A;Braakhuis, A;Harrison, LC
通过黏膜途径给药，如口服或鼻腔给药，可诱导特异性免疫耐受，已被用作治疗包括1型糖尿病在内的自身免疫性疾病的合理基础。然而，最近，口服抗原仅仅被证明能诱导CD8细胞毒性T淋巴细胞(CTL)，能够引起自身免疫性糖尿病。在这份报告中，我们研究了几种粘膜途径诱导CTL和自身免疫性糖尿病的能力，目的是确定能够最大限度地耐受和最大限度减少CTL生成的方法。在正常C57BL/6小鼠中，通过口服或鼻腔途径或雾化吸入的卵清蛋白(OVA)能够在高剂量和低剂量方案中启动CTL免疫。为了解决这些CTL与自身免疫性疾病的相关性，研究人员给在其胰岛β细胞中转基因表达这种抗原的小鼠注射了卵清蛋白。无论抗原剂量或递送途径如何，粘膜OVA都会引发糖尿病，特别是在鼻腔给药后。这些发现表明，CTL免疫很可能是黏膜抗原传递的结果，无论采用哪种方案，在临床应用粘膜耐受预防自身免疫性疾病时都应考虑CTL免疫。
Administration of antigens via mucosal routes, such as orally or intranasally, can induce specific immunological tolerance and has been used as a rational basis for the treatment of autoimmune diseases, including type 1 diabetes. Recently, however, orally delivered antigens mere shown to induce CD8 cytotoxic T-lymphocytes (CTLs) capable of causing autoimmune diabetes. In this report, we have examined several mucosal routes for their ability to induce CTLs and autoimmune diabetes, with the aim of identifying approaches that would maximize tolerance and minimize CTL generation, In normal C57BL/6 mice, ovalbumin (OVA) delivered by either the oral or nasal routes or by aerosol inhalation was able to prime CTL immunity in both high- and low-dose regimens. To address the relevance of these CTLs to autoimmune disease, OVA was given to mice that transgenically expressed this antigen in their pancreatic beta -cells. Irrespective of antigen dose or the route of delivery, mucosal OVA triggered diabetes, particularly after intranasal administration. These findings suggest that CTL immunity is likely to be a consequence of mucosal antigen delivery, regardless of the regimen, and should be considered in the clinical application of mucosal tolerance to autoimmune disease prevention.