Differential localization of colitogenic Th1 and Th2 cells monospecific to a microflora-associated antigen in mice.
Differential localization of colitogenic Th1 and Th2 cells monospecific to a microflora-associated antigen in mice.
复制标题
小鼠中对微生物群相关抗原具有单特异性的致结肠炎 Th1 和 Th2 细胞的差异定位。
DOI：
10.1053/gast.2002.37049
复制
发表时间：
2002
期刊：
影响因子：
29.4
通讯作者：
Y. Wakatsuki
中科院分区：
文献类型：
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作者：
Masaru Yoshida;Y. Shirai;Tomohiro Watanabe;M. Yamori;Y. Iwakura;T. Chiba;T. Kita;Y. Wakatsuki
背景与目标
T 细胞的克隆扩增与炎症性肠病相关，这表明 T 细胞的抗原激活。我们研究了引入特定微生物区系的 CD4 T 细胞是否会引发结肠炎，并评估了致结肠炎 CD4 T 细胞的细胞因子需求。
方法
严重联合免疫缺陷病 (SCID) 小鼠用 CD4 T 细胞重建，这些细胞要么缺乏白细胞介素 (IL)-4/干扰素 (IFN)-γ 产生，要么在体外分化为 T 辅助细胞 (Th) 1/Th 2，并带有卵清蛋白 (OVA) 特异性的转基因 T 细胞受体 (TCR)，然后接种产生 OVA (ECOVA) 的大肠杆菌。评估结肠炎的临床和组织学表现。
结果
具有 ECOVA 定植和 OVA 特异性 CD4 T 细胞的小鼠出现结肠炎，其组织学特征为单核细胞局灶性浸润、隐窝破坏和杯状细胞丢失。此外，在预先存在的淋巴滤泡中开始浸润。 Th1 和 IL-4 缺陷型 T 细胞广泛分布于固有层和粘膜下层，而 Th2 和 IFN-γ 缺陷型 T 细胞优先分布于淋巴滤泡中。
结论
一种与结肠组织不发生交叉反应的微生物相关抗原可以驱动抗原特异性 CD4 T 细胞在 SCID 小鼠中引起结肠炎。尽管效应 CD4 T 细胞中存在 IFN-γ 和 IL-4 并不是结肠炎发生的绝对必要条件，但它们似乎通过调节效应 T 细胞的迁移来部分调节结肠炎。
BACKGROUND & AIMS
Clonal expansion of T cells is associated with inflammatory bowel diseases, which indicates antigenic activation of the T cells. We investigated whether the introduction of CD4 T cells specific to a microflora would initiate colitis and assessed the cytokine requirements for colitogenic CD4 T cells.
METHODS
Severe combined immunodeficiency disease (SCID) mice were reconstituted with CD4 T cells, which were either deficient in interleukin (IL)-4/interferon (IFN)-gamma production or differentiated in vitro to T-helper (Th) 1/Th 2 and bearing a transgenic T-cell receptor (TCR) specific to ovalbumin (OVA), and then inoculated with an Escherichia coli-producing OVA (ECOVA). Clinical and histologic manifestations of colitis were assessed.
RESULTS
Mice with ECOVA colonization and OVA-specific CD4 T cells developed colitis with histologic features of focal infiltration by mononuclear cells, destruction of crypts, and loss of goblet cells. Further, infiltration was initiated in pre-existing lymph follicles. Th1- and IL-4 deficient T cells were diffusely localized in the lamina propria and submucosa, whereas Th2- and IFN-gamma-deficient T cells were localized preferentially in lymph follicles.
CONCLUSIONS
A microbe-associated antigen, non-cross-reactive to colonic tissue, can drive antigen-specific CD4 T cells to cause colitis in SCID mice. Although the presence of IFN-gamma and IL-4 in the effector CD4 T cells was not an absolute requirement for the development of colitis, they seemed to regulate it in part by modulating migration of the effector T cells.
Yoshida M、Wakatsuki Y、Kobayashi Y、Itoh T、Murakami K、Usui T、Chiba T、Kita T：“幽门螺杆菌新型膜相关抗原蛋白的克隆和表征。”感染免疫。
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