T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis.
T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis.
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DOI：
10.1084/jem.2001889
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发表时间：
2002-01-07
期刊：
影响因子：
--
通讯作者：
Weaver CT
中科院分区：
文献类型：
--
作者：
Iqbal N;Oliver JR;Wagner FH;Lazenby AS;Elson CO;Weaver CT
对肠道细菌的失调的T细胞应答已经被认为是啮齿动物结肠炎模型中的常见发病机制。然而，引起疾病的细菌种类和T细胞特异性的定义很差。我们已经开发了一个模型系统，其中定义了靶抗原、细菌宿主和相应的T细胞特异性。将来自DO11.RAG-2−/− TCR转基因小鼠的OVA特异性T细胞转移到RAG-2−/−受体中，受体的肠道用表达OVA或对照大肠杆菌定殖。将抗原初始DO11.RAG-2−/− T细胞转移到用OVA-E定殖的受体中。大肠杆菌导致增强肠道募集和细胞周期的OVA特异性T细胞，但没有发展的疾病。相反，极化的辅助性T细胞（Th）1和Th 2细胞群的转移导致了OVA表达的受体的严重消瘦和结肠炎，而对照组则没有。杆菌由Th 1和Th 2转移引起的疾病的组织病理学特征是不同的，但疾病的严重程度是可比的。由Th 1和Th 2转移引起的疾病依赖于细菌相关的OVA。这些结果表明，单一的细菌相关抗原可以驱动由Th 1和Th 2细胞介导的结肠炎的进展，并提供了一个新的模型，用于了解T细胞之间的免疫调节相互作用响应肠道花抗原。
Dysregulated T cell responses to enteric bacteria have been implicated as a common mechanism underlying pathogenesis in rodent models of colitis. However, the bacterial species and T cell specificities that induce disease have been poorly defined. We have developed a model system in which target antigen, bacterial host, and corresponding T cell specificity are defined. OVA-specific T cells from DO11.RAG-2−/− TCR transgenic mice were transferred into RAG-2−/− recipients whose intestinal tracts were colonized with OVA-expressing or control Escherichia coli. Transfer of antigen-naive DO11.RAG-2−/− T cells into recipients colonized with OVA-E. coli resulted in enhanced intestinal recruitment and cell cycling of OVA-specific T cells; however, there was no development of disease. In contrast, transfer of polarized T helper (Th) 1 and Th2 populations resulted in severe wasting and colitis in recipients colonized with OVA-expressing but not control E. coli. The histopathologic features of disease induced by Th1 and Th2 transfers were distinct, but disease severity was comparable. Induction of disease by both Th1 and Th2 transfers was dependent on bacterially associated OVA. These results establish that a single bacterially associated antigen can drive the progression of colitis mediated by both Th1 and Th2 cells and provide a new model for understanding the immunoregulatory interactions between T cells responsive to gut floral antigens.
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DOI：
10.1073/pnas.92.16.7565
发表时间：
1995-08-01
影响因子：
11.1
作者：
BUCY, RP;KARR, L;WEAVER, CT
通讯作者：
WEAVER, CT
影响因子：
2.6
作者：
FAIRWEATHER, NF;CHATFIELD, SN;DOUGAN, G
通讯作者：
DOUGAN, G
影响因子：
32.4
作者：
KEARNEY, ER;PAPE, KA;JENKINS, MK
通讯作者：
JENKINS, MK
影响因子：
3.1
作者：
Cahill, RJ;Foltz, CJ;Schauer, DB
通讯作者：
Schauer, DB
DOI：
10.1038/nbt0892-888
发表时间：
1992-08-01
期刊：
BIO-TECHNOLOGY
影响因子：
--
作者：
CHATFIELD, SN;CHARLES, IG;FAIRWEATHER, NF
通讯作者：
FAIRWEATHER, NF