Thymus‐dependent monoclonal antibody‐induced protection from transferred diabetes

Thymus‐dependent monoclonal antibody‐induced protection from transferred diabetes
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胸腺依赖性单克隆抗体诱导的转移性糖尿病保护

DOI:
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发表时间:
1998
影响因子:
5.4
通讯作者:
A. Cooke
A. Cooke
中科院分区:
医学3区
文献类型:
--
作者:
N. Parish;L. Bowie;Silvia Zusman Harach;J. Phillips;A. Cooke

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已经确定,短期非消耗性(nd)抗CD4单克隆抗体(mAb)可以为非肥胖糖尿病(NOD)小鼠提供长期胰岛素依赖性糖尿病(IDDM)保护。由于越来越明显的是,CD8+ T细胞在IDDM的发展中起着重要作用,我们研究了相同同种型的抗CD8 mAb(YTS 105)在NOD小鼠自发性和诱导性IDDM中的作用。用YTS 105治疗3周能够长期防止IDDM的转移,并且还显著减少雌性NOD小鼠中的自发性IDDM。研究了胸腺在这些抗体诱导耐受中的作用。在成年转移模型中,胸腺切除的NOD小鼠与其胸腺正常的对应小鼠不同,没有受到YTS 105治疗的长期保护,并且在治疗后不久开始变得明显糖尿病。当使用nd抗CD4 mAb时也是如此。对自发性疾病的保护并没有受到胸腺切除术的同样影响。在转移模型中观察到的胸腺效应的原因,以及可能解释对比结果的两种模型之间的差异进行了讨论。
It is well established that long‐term protection from insulin‐dependent diabetes mellitus (IDDM) can be afforded to non‐obese diabetic (NOD) mice by a short course of non‐depleting (nd) anti‐CD4 monoclonal antibodies (mAb). Since it is increasingly apparent that the CD8+ T cell plays a prominent role in the development of IDDM, we have investigated the effect of an anti‐CD8 mAb (YTS 105) of the same isotype in both spontaneous and induced IDDM in NOD mice. Treatment with YTS 105 for 3 weeks was able to prevent the transfer of IDDM for a long period, and also substantially reduced spontaneous IDDM in female NOD mice. The role of the thymus in tolerance induction by these antibodies was studied. In the adult transfer model, thymectomized NOD mice, unlike their euthymic counterparts, were not protected long‐term by treatment with YTS 105, and began to become overtly diabetic shortly after treatment. This was also true when the nd anti‐CD4 mAb was used. Protection from spontaneous disease was not affected in the same way by thymectomy. The reasons for the observed effect of the thymus in the transfer model, and the differences between the two models that may explain the contrasting results are discussed.
DOI: 10.4049/jimmunol.140.1.52
发表时间: 1988-01
影响因子: 4.4
作者:
B. J. Miller;M. Appel;J. O'neil;L. Wicker
通讯作者: B. J. Miller;M. Appel;J. O'neil;L. Wicker