小鼠胎儿暴露于自身抗原会诱发非致病性自身免疫

IF 4.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jeng-Chang Chen , Liang-Shiou Ou , Ming-Ling Kuo , Li-Yun Tseng , Hsueh-Ling Chang
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引用次数: 0

摘要

背景和目的自身免疫是指针对个体细胞或组织结构分子(称为自身抗原或自身抗原)的自身抗体和自身反应性淋巴细胞的存在。在没有自身免疫疾病的情况下,自身免疫也可能存在。方法通过经子宫途径向妊娠第 14 天的小鼠胎儿腹腔内注射分级剂量的小鼠甲状腺过氧化物酶(TPO)肽或 II 型胶原蛋白(CII)。结果一个月大时,受体血清中抗TPO或CII IgG2a的水平并不明显,直到宫内注射了0.5微克TPO或5.0微克CII。血清中的抗血小板生成素或 CII IgG2a 在出生后至少持续 2 到 4 个月。在自身抗体升高的受体中,他们的淋巴细胞也显示出对 TPO 或 CII 的特异性增殖反应。结论胎儿暴露于游离自身抗原可能具有免疫原性,这为自身抗体和自身反应性淋巴细胞在子宫内的来源提供了新的线索。自身免疫的发展需要胎儿暴露于自身抗原的阈值强度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autoantigen Exposure in Murine Fetuses Elicited Nonpathogenic Autoimmunity

Background and aim

Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood.

Methods

Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis.

Results

At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG2a was enhanced by postnatal TPO or CII challenge.

Conclusion

Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus.

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来源期刊
Archives of Medical Research
Archives of Medical Research 医学-医学:研究与实验
CiteScore
12.50
自引率
0.00%
发文量
84
审稿时长
28 days
期刊介绍: Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.
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