Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4+CD25+ T cells
Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4+CD25+ T cells
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DOI：
10.1006/jaut.2000.0473
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发表时间：
2001-03-01
影响因子：
12.8
通讯作者：
Cantor, H
中科院分区：
文献类型：
--
作者：
Suri-Payer, E;Cantor, H
小鼠自身免疫性胃炎，诱导新生儿胸腺切除术或注射CD 25-耗尽淋巴细胞到nu/nu受体，其特征在于炎性浸润到胃粘膜，壁细胞破坏和循环抗壁细胞抗体。使用RAG-2（-/-）小鼠作为受体，我们确定疾病的诱导依赖于CD 4（+）CD 25（-）效应细胞，而预防依赖于CD 4（+）CD 25（+）调节细胞;两者都不需要CD 8细胞或B细胞的参与。胃炎的严重程度取决于CD 4（+）CD 25（-）效应T细胞的细胞因子库。与野生型或IL-10（-/-）效应T细胞受体相比，IL-4（-/-）T细胞受体发生更严重的胃炎，INF-γ（-/-）T细胞受体发生更轻的疾病。在IL-12不存在的情况下，不发生Gastrointestinal。预防胃炎不需要IL-4或IL-10，因为IL-4（-/-）或IL-10（-/-）小鼠的CD 4（+）CD 25（+）细胞完全消除了疾病过程。CD 4（+）CD 25（+）细胞也保护RAG-2（-/-）受体免于结肠炎，并且抑制活性部分依赖于IL-10表达。这些发现强调了CD 4（+）CD 25（+）调节性T细胞在保护免受几种自身免疫综合征中的关键作用，并描述了IL-10对胃炎和结肠炎背景下CD 4（+）CD 25（+）Treg活性的不同贡献。(C)北京：科学出版社.
Murine autoimmune gastritis, induced by neonatal thymectomy or the injection of CD25-depleted lymphocytes into nu/nu recipients, is characterized by an inflammatory infiltrate into the gastric mucose, parietal cell destruction and circulating anti-parietal cell antibodies. Using RAG-2(-/-) mice as recipients, we determined that the induction of disease relies on CD4(+)CD25(-) effector cells and prevention relies on CD4(+)CD25(+) regulatory cells; neither requires participation of CD8 cells or B cells. The severity of gastritis was dependent on the cytokine repertoire of CD4(+)CD25(-) effector T cells. Recipients of IL-4(-/-) T cells developed more severe gastritis and recipients of INF-gamma (-/-) T cells developed milder disease than recipients of wildtype or IL-10(-/-) effector T cells. Gastritis did not develop in the absence of IL-12. Protection from gastritis does not require either IL-4 or IL-10 because CD4(+)CD25(+) cells from IL-4(-/-) or IL-10(-/-) mice completely abrogated the disease process. CD4(+)CD25(+) cells also protected RAG-2(-/-) recipients from colitis and inhibitory activity was partially dependent on IL-10 expression. These findings highlight the critical role of CD4(+)CD25(+) regulatory T cells in protection from several autoimmune syndromes and delineate the differential contribution of IL-10 to CD4(+)CD25(+) Treg activity in the settings of gastritis and colitis. (C) 2001 Academic Press.