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口服S抗原和合成肽对实验性自身免疫性葡萄膜视网膜炎的抑制作用。

Inhibition of experimental autoimmune uveoretinitis by oral administration of S-antigen and synthetic peptides.

作者信息

Vrabec T R, Gregerson D S, Dua H S, Donoso L A

机构信息

Retina Service, Wills Eye Hospital, Philadelphia, PA 19107.

出版信息

Autoimmunity. 1992;12(3):175-84. doi: 10.3109/08916939209148457.

DOI:10.3109/08916939209148457
PMID:1343765
Abstract

S-Antigen, a photoreceptor cell protein, is highly efficient in inducing experimental autoimmune uveoretinitis (EAU), a severe inflammation of the uveal tract and retina of the eye. S-Antigen and six synthetic peptides, all of which correspond to known T-cell or B-cell recognition sites, were tested for their ability to induce oral tolerance to EAU in LEW rats. Feeding three 1-mg doses of native S-Antigen or three doses of one synthetic peptide, designated BSA(343-362) (200 micrograms per dose), reduced the incidence and severity of EAU induced by immunization with 50 micrograms of S-Antigen. Another peptide, BSA(270-289), was able to inhibit EAU only when a low dose (10 micrograms) of the uveitogenic S-Antigen was used to induce EAU. Animals which received 200 micrograms doses of four other immunologically active peptides, BSA(31-51), BSA(143-162), BSA(303-327) and BSA(333-352), were not significantly protected. Furthermore, animals fed BSA(343-362) were significantly less susceptible to EAU induced by adoptive transfer (tEAU) of the uveitogenic R9 T-cell lines. Con A-activated lymphocytes purified from spleens of rats fed peptide BSA(343-362) transferred partial resistance to tEAU induced by adoptive transfer of R9 line cells. The resistance of orally tolerized rats to induction of EAU by adoptive transfer of an activated, pathogenic T-cell line, and the ability of lymphocytes from orally-tolerized animals to transfer resistance to tEAU shows that effector mechanisms can be inhibited by oral feeding as well as the afferent mechanisms reported here and elsewhere. Circulating levels of IgG specific for S-Antigen were not affected by feeding any of the peptides.

摘要

S抗原是一种光感受器细胞蛋白,在诱导实验性自身免疫性葡萄膜视网膜炎(EAU)方面效率极高,EAU是一种眼部葡萄膜和视网膜的严重炎症。对S抗原和六种合成肽进行了测试,所有这些肽都对应已知的T细胞或B细胞识别位点,以研究它们在LEW大鼠中诱导对EAU口服耐受的能力。喂食三剂1毫克的天然S抗原或三剂一种名为BSA(343 - 362)的合成肽(每剂200微克),可降低用50微克S抗原免疫诱导的EAU的发病率和严重程度。另一种肽BSA(270 - 289),只有在使用低剂量(10微克)的致葡萄膜炎S抗原诱导EAU时才能抑制EAU。接受200微克剂量的其他四种具有免疫活性的肽BSA(31 - 51)、BSA(143 - 162)、BSA(303 - 327)和BSA(333 - 352)的动物没有得到显著保护。此外,喂食BSA(343 - 362)的动物对致葡萄膜炎R9 T细胞系的过继转移(tEAU)诱导的EAU明显更不易感。从喂食肽BSA(343 - 362)的大鼠脾脏中纯化的伴刀豆球蛋白A激活的淋巴细胞转移了对R9系细胞过继转移诱导的tEAU的部分抗性。口服耐受的大鼠对活化的致病性T细胞系过继转移诱导的EAU的抗性,以及口服耐受动物的淋巴细胞转移对tEAU抗性的能力表明,效应机制可以通过口服喂养以及本文和其他地方报道的传入机制来抑制。喂食任何一种肽都不会影响针对S抗原的循环IgG水平。

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