Clonality, activated antigen-specific CD8(+) T cells, and development of autoimmune cholangitis in dnTGFβRII mice.
Clonality, activated antigen-specific CD8(+) T cells, and development of autoimmune cholangitis in dnTGFβRII mice.
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DOI：
10.1002/hep.26418
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发表时间：
2013-09
期刊：
影响因子：
13.5
通讯作者：
Gershwin, M. Eric
中科院分区：
文献类型：
--
作者：
Kawata, Kazuhito;Yang, Guo-Xiang;Ando, Yugo;Tanaka, Hajime;Zhang, Weici;Kobayashi, Yoshimasa;Tsuneyama, Koichi;Leung, Patrick S. C.;Lian, Zhe-Xiong;Ridgway, William M.;Ansari, Aftab A.;He, Xiao-Song;Gershwin, M. Eric
有几种小鼠模型被描述具有与人类原发性胆汁性肝硬化（PBC）相似的特征。在这些模型中，具有与PBC最接近的血清学特征的是具有显性负性转化生长因子β受体II（dnTGFβRII）的T细胞限制性表达的小鼠。我们的工作已经证明来自dnTGFβRII小鼠的CD 8 + T细胞将自身免疫性胆管炎转移到Rag 1-/-受体。然而，尚不清楚自身免疫性胆管炎是否继发于CD 8 + T细胞内的内在功能或由于产生CD 8 + T细胞的异常TGFβR环境。为了解决这一机制问题，我们利用了我们的dnTGFβRII、OT-I/Rag 1-/-、OT-II/Rag 1-/-小鼠，并另外产生了OT-I/dnTGF β RII/Rag 1-/-和OT-II/dnTGFβRII/Rag 1-/-小鼠，其中整个T细胞库分别被卵清蛋白（OVA）特异性CD 8+或CD 4 + T细胞取代。重要的是，亲代OT-I/dnTGFβRII/Rag 1-/-小鼠和/或OT-II/dnTGFβRII/Rag 1-/-小鼠均未发生胆管炎。然而，过继转移证明，只有来自dnTGFβRII小鼠的CD 8 + T细胞的转移，而不是来自OT-I/Rag -/-小鼠或来自OT-I/dnTGFβRII/Rag 1-/-小鼠的CD 8 + T细胞的转移。这些数据并非继发于缺乏CD 4 + T细胞帮助，因为来自OT-I/dnTGFβRII/Rag 1-/-的CD 8 + T细胞和来自OT II/dnTGFβRII/Rag 1-/-的CD 4 + T细胞或来自OT-I/dnTGFβRII/Rag 1-/-的CD 8 + T细胞与来自OT-II/Rag 1-/-小鼠的CD 4 + T细胞的组合未能转移疾病。总之，除了靶向胆管细胞的克隆性CD 8 + T细胞外，有缺陷的TGFβRII信号传导是诱导自身免疫性胆管炎所必需的。
There are several murine models described with features similar to human primary biliary cirrhosis (PBC). Amongst these models, the one which has the closest serologic features to PBC is a mouse with a T cell-restricted expression of the dominant negative transforming growth factor β receptor type II (dnTGFβRII). Our work has demonstrated that CD8+ T cells from dnTGFβRII mice transfer autoimmune cholangitis to Rag1-/- recipients. However, it remained unclear whether the autoimmune cholangitis was secondary to an intrinsic function within CD8+ T cells or due to the abnormal TGFβR environment within which CD8+ T cells were generated. To address this mechanistic issue, we utilized our dnTGFβRII, OT-I/Rag1-/-, OT-II/Rag1-/- mice and in addition generated OT-I/dnTGFβRII/Rag1-/-, and OT-II/dnTGFβRII/Rag1-/- mice in which the entire T cell repertoire was replaced with ovalbumin (OVA) specific CD8+ or CD4+ T cells, respectively. Importantly, neither the parental OT-I/dnTGFβRII/Rag1-/- mice and/or OT-II/dnTGFβRII/Rag1-/- mice developed cholangitis. However, adoptive transfer demonstrated that only transfer of CD8+ T cells from dnTGFβRII mice but not CD8+ T cells from OT-I/Rag -/- mice or from OT-I/dnTGFβRII/Rag1-/- mice transferred disease. These data were not secondary to absence of CD4+ T cell help since a combination of CD8+ T cells from OT-I/dnTGFβRII/Rag1-/- and CD4+ T cells from OT II/dnTGFβRII/Rag1-/- or CD8+ T cells from OT-I/dnTGFβRII/Rag1-/- with CD4+ T cells from OT-II/Rag1-/- mice failed to transfer disease. In conclusion, defective TGFβRII signaling, in addition to clonal CD8+ T cells that target biliary cells, are required for induction of autoimmune cholangitis.
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HLA DRB4 0101丙酮酸丙酮酸脱氢酶复合物的限制性免疫主导T细胞自动tip虫中胆汁肝硬化：人体自身免疫性疾病中分子模仿的证据。
DOI：
10.1084/jem.181.5.1835
发表时间：
1995-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Shimoda S;Nakamura M;Ishibashi H;Hayashida K;Niho Y
通讯作者：
Niho Y
影响因子：
13.5
作者：
Lleo, Ana;Selmi, Carlo;Invernizzi, Pietro;Podda, Mauro;Coppel, Ross L.;Maclay, Ian R.;Gores, Gregory J.;Ansari, Aftab A.;de Water, Judy Van;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
影响因子：
13.5
作者：
Ando, Yugo;Yang, Guo-Xiang;Tsuda, Masanobu;Kawata, Kazuhito;Zhang, Weici;Nakajima, Takahiko;Tsuneyama, Koichi;Leung, Patrick;Lian, Zhe-Xiong;Okazaki, Kazuichi;Ridgway, William M.;Norman, Gary L.;Ansari, Aftab A.;He, Xiao-Song;Coppel, Ross L.;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
影响因子：
6
作者：
Polakos, NK;Cornejo, JC;Pierce, RH
通讯作者：
Pierce, RH
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA