Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide.
Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide.
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小鼠的器官特异性自身免疫，其 T 细胞库由单一抗原肽形成。
DOI：
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发表时间：
2001
影响因子：
15.9
通讯作者：
T. Sasazuki
中科院分区：
文献类型：
--
作者：
T. Oono;Y. Fukui;S. Masuko;O. Hashimoto;T. Ueno;T. Sanui;A. Inayoshi;M. Noda;M. Sata;T. Sasazuki
器官特异性自身免疫性疾病被认为是T细胞对与MHC分子结合的器官特异性自身肽的应答的结果。与此相反，我们在这里报告，缺乏MHC I类表达和表达MHC II类I-A（B）分子，提出只有一个单一的肽（E α 52-68）的转基因小鼠自发发展外周神经系统特异性自身免疫性疾病与实验性过敏性神经炎中发现的许多组织病理学特征。使用易感和耐药品系产生的相互骨髓嵌合体显示，骨髓来源的细胞决定疾病易感性。虽然I-A（B）-E α 52-68复合物在外周的表达在两个系中都很容易检测到，但其在负责耐受诱导的胸腺树突状细胞上的表达在敏感系中明显低于在抗性系中。与此一致，在易感品系中发现了可被I-A（B）-E α 52-68复合物激活的CD 4（+）T细胞，但在抗性品系中未发现。这种CD 4（+）T细胞通过过继转移将疾病传给抗性系，并且施用对I-A（B）-E α 52-68复合物特异的Ab抑制了易感系中的疾病表现。这些结果表明，疾病的发展涉及全身性T细胞对I-A（B）-E α 52-68复合物的反应性，这可能是由不完全阴性胸腺细胞选择引起的。
Organ-specific autoimmune diseases have been postulated to be the result of T cell response against organ-specific self-peptides bound to MHC molecules. Contrary to this paradigm, we report here that transgenic mice lacking MHC class I expression and expressing an MHC class II I-A(b) molecule that presents only a single peptide (E alpha 52-68) spontaneously develops peripheral nervous system-specific autoimmune disease with many of the histopathological features found in experimental allergic neuritis. Reciprocal bone marrow chimeras produced using susceptible and resistant lines revealed that bone marrow-derived cells determined disease susceptibility. While the expression of the I-A(b)-E alpha 52-68 complex in the periphery was readily detectable in both lines, its expression on thymic dendritic cells responsible for tolerance induction was markedly lower in the susceptible line than in the resistant line. Consistent with this, CD4(+) T cells that can be activated by the I-A(b)-E alpha 52-68 complex were found in the susceptible line, but not in the resistant line. Such CD4(+) T cells conferred the disease to the resistant line by adoptive transfer, and administration of Ab specific for the I-A(b)-E alpha 52-68 complex inhibited disease manifestation in the susceptible line. These results indicate that disease development involves systemic T cell reactivity to I-A(b)-E alpha 52-68 complex, probably caused by incomplete negative thymocyte selection.
自身免疫的基础：第一部分。异常自我识别的机制。
DOI：
10.1016/0167-5699(95)80095-6
发表时间：
1995
期刊：
Immunology today.
影响因子：
--
作者：
Theofilopoulos,AN
通讯作者：
Theofilopoulos,AN
活化 T 细胞免疫产生的 Ia 糖蛋白特异性单克隆抗体：T 细胞结合 Ia 抗原作为免疫调节 T 细胞靶标的可能作用。
DOI：
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发表时间：
1984
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
JanewayJr,CA;Conrad,PJ;Lerner,EA;Babich,J;Wettstein,P;Murphy,DB
通讯作者：
Murphy,DB