Urothelial antigen-specific CD4+ T cells function as direct effector cells and induce bladder autoimmune inflammation independent of CD8+ T cells.
Urothelial antigen-specific CD4+ T cells function as direct effector cells and induce bladder autoimmune inflammation independent of CD8+ T cells.
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由于缺乏合适的动物模型，CD4+T细胞在膀胱自身免疫性炎症中的作用尚未明确。我们研究了转基因尿路上皮卵蛋白(OVA)转基因小鼠对膀胱尿路上皮卵清蛋白(OVA)的反应。膀胱尿路上皮OVA的表达使小鼠对OVA没有反应，并导致抗原特异性CD4+T细胞的快速清除。过继转移幼稚的OVA特异性的CD4+T细胞导致外源性T细胞的增殖、激活和膀胱浸润，但没有诱导炎症。相比之下，过继转移预先激活的OVA特异性CD4+T细胞会导致膀胱炎症。研究进一步证明，CD_4~+T细胞可诱导CD_8~+T细胞耗竭或重组酶激活基因-1(RAG-1−/−)缺失的小鼠膀胱炎。这些结果表明，尿路上皮抗原特异性的CD4+T细胞可以作为直接效应细胞诱导膀胱自身免疫性炎症，而不依赖于CD8+T细胞。
The role of CD4+ T cells in bladder autoimmune inflammation has not been identified due to the lack of a proper animal model. We investigated CD4+ T cell responses to bladder urothelial ovalbumin (OVA), a model self-antigen (Ag), in transgenic URO-OVA mice. The expression of bladder urothelial OVA rendered mice unresponsive to OVA and resulted in quick clearance of Ag-specific CD4+ T cells. Adoptive transfer of naïve OVA-specific CD4+ T cells led to exogenous T cell proliferation, activation, and bladder infiltration but no inflammatory induction. In contrast, adoptive transfer of pre-activated OVA-specific CD4+ T cells induced bladder inflammation. Studies further demonstrated that CD4+ T cells induced bladder inflammation in URO-OVA mice depleted of CD8+ T cells or deficient in the recombinase activating gene-1 (Rag-1−/−). These results indicate that urothelial Ag-specific CD4+ T cells can function as direct effector cells to induce bladder autoimmune inflammation independent of CD8+ T cells.
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影响因子：
4.4
作者：
Amend, Bastian;Doster, Hong;Bischof, Felix
通讯作者：
Bischof, Felix
DOI：
10.1084/jem.186.12.2057
发表时间：
1997-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kurts C;Carbone FR;Barnden M;Blanas E;Allison J;Heath WR;Miller JF
通讯作者：
Miller JF
DOI：
10.1111/j.1464-410x.1994.tb07635.x
发表时间：
1994-05-01
期刊：
BRITISH JOURNAL OF UROLOGY
影响因子：
--
作者：
CHRISTMAS, TJ
通讯作者：
CHRISTMAS, TJ
影响因子：
6.4
作者：
Elzey, BD;Siemens, DR;Lubaroff, DM
通讯作者：
Lubaroff, DM
影响因子：
4.4
作者：
Cantor, J;Haskins, K
通讯作者：
Haskins, K