Suri-Payer E, Cantor H
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, SM722, Boston, MA 02115, USA.
J Autoimmun. 2001 Mar;16(2):115-23. doi: 10.1006/jaut.2000.0473.
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 mucosa, 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.
通过新生期胸腺切除或向裸鼠受体注射去除CD25的淋巴细胞诱导的小鼠自身免疫性胃炎，其特征为胃黏膜出现炎症浸润、壁细胞破坏以及循环抗壁细胞抗体。以RAG-2(-/-)小鼠作为受体，我们确定疾病的诱导依赖于CD4(+)CD25(-)效应细胞，而预防则依赖于CD4(+)CD25(+)调节细胞；两者均不需要CD8细胞或B细胞的参与。胃炎的严重程度取决于CD4(+)CD25(-)效应T细胞的细胞因子谱。与野生型或IL-10(-/-)效应T细胞的受体相比，IL-4(-/-)T细胞的受体发生更严重的胃炎，而INF-γ(-/-)T细胞的受体发生的疾病较轻。在没有IL-12的情况下不会发生胃炎。预防胃炎既不需要IL-4也不需要IL-10，因为来自IL-4(-/-)或IL-10(-/-)小鼠的CD4(+)CD25(+)细胞完全消除了疾病进程。CD4(+)CD25(+)细胞还保护RAG-2(-/-)受体免受结肠炎的影响，并且抑制活性部分依赖于IL-10的表达。这些发现突出了CD4(+)CD25(+)调节性T细胞在预防多种自身免疫综合征中的关键作用，并阐明了IL-10在胃炎和结肠炎背景下对CD4(+)CD25(+)Treg活性的不同贡献。
