Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells1
Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells1
复制标题
使用与霍乱毒素 B 亚基缀合的抗原进行口服耐受诱导可生成 Foxp3+CD25+ 和 Foxp3−CD25− CD4+ 调节性 T 细胞1
作者：
Jia;S. Raghavan;Å. Sjöling;S. Lundin;J. Holmgren
口服偶联霍乱毒素B亚单位(CTB)的抗原可有效地诱导外周免疫耐受。我们调查了这种口服耐受在多大程度上是由CD25+CD4+调节性T细胞(Treg)介导的。结果发现，灌胃给予卵清蛋白/四环素结合物后，小鼠脾组织中总Treg、KJ1-26+Treg和CTLA-4+Treg均有不同程度的增加，血清中的转化生长因子-β也有所增加。这可以通过联合注射霍乱毒素或用抗转化生长因子-β单抗治疗来消除。CD2 5+Treg和CD2 5−CD4+T细胞在体外能有效地抑制效应T细胞的增殖和IL-2的产生。过继移植后，两个T细胞群也抑制体内OVA特异性T细胞和迟发性超敏反应。经OVA/CTB处理的小鼠CD25+Treg表达Foxp3，治疗后CD25+Foxp3+Treg显著增加。此外，在过继接受高纯度Foxp3Treg的RAG1−/−小鼠中，−/−可有效地诱导CD25+Treg细胞，其表达Foxp3的能力强于自然发育的Treg，并且具有更强的抑制效应器OT-II T细胞增殖的能力。剩余的CD25Foxp3 T细胞群也对卵清蛋白/四环素治疗有抑制作用，但不表达−。我们的结果表明，CTB结合的抗原诱导的口服耐受与转化生长因子β的增加、Foxp3+和CTLA4+CD25+Treg的频率和抑制能力以及Foxp3+和Foxp3−CD25CD4+−+Treg的产生有关。
Oral administration of Ag coupled to cholera toxin B subunit (CTB) efficiently induces peripheral immunological tolerance. We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (Treg). We found that total Treg, KJ1–26+ Treg and CTLA-4+ Treg were all increased in Peyer’s patches, mesenteric lymph nodes, and, to a lesser extent, in spleen of mice after intragastric administration of OVA/CTB conjugate, which also increased TGF-β in serum. This could be abolished by coadministering cholera toxin or by treatment with anti-TGF-β mAb. CD25+ Treg, but also CD25−CD4+ T cells from OVA/CTB-treated BALB/c or DO11.10 mice efficiently suppressed effector T cell proliferation and IL-2 production in vitro. Following adoptive transfer, both T cell populations also suppressed OVA-specific T cell and delayed-type hypersensitivity responses in vivo. Foxp3 was strongly expressed by CD25+ Treg from OVA/CTB-treated mice, and treatment also markedly expanded CD25+Foxp3+ Treg. Furthermore, in Rag1−/− mice that had adoptively received highly purified Foxp3−CD25−CD4+ OT-II T cells OVA/CTB feeding efficiently induced CD25+ Treg cells, which expressed Foxp3 more strongly than naturally developing Treg and also had stronger ability to suppress effector OT-II T cell proliferation. A remaining CD25− T cell population, which also became suppressive in response to OVA/CTB treatment, did not express Foxp3. Our results demonstrate that oral tolerance induced by CTB-conjugated Ag is associated with increase in TGF-β and in both the frequency and suppressive capacity of Foxp3+ and CTLA-4+ CD25+ Treg together with the generation of both Foxp3+ and Foxp3−CD25− CD4+ Treg.
霍乱毒素喂养不会诱导小鼠的口服耐受性，并且消除了对不相关蛋白抗原的口服耐受性。
DOI：
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发表时间：
1984
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Elson,CO;Ealding,W
通讯作者：
Ealding,W
口服耐受的 CD8 缺陷小鼠缺乏局部抑制揭示了 CD8 T 细胞在正常肠粘膜中的关键调节作用。
DOI：
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发表时间：
1998
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Grdic,D;Hörnquist,E;Kjerrulf,M;Lycke,NY
通讯作者：
Lycke,NY
实验性自身免疫性脑脊髓炎的口服耐受。
DOI：
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发表时间：
1991
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Whitacre,CC;Gienapp,IE;Orosz,CG;Bitar,DM
通讯作者：
Bitar,DM