Interleukin-10-secreting Peyer's patch cells are responsible for active suppression in low-dose oral tolerance
Interleukin-10-secreting Peyer's patch cells are responsible for active suppression in low-dose oral tolerance
复制标题
DOI：
10.1046/j.1365-2567.2001.01265.x
复制
发表时间：
2001-08-01
期刊：
影响因子：
6.4
通讯作者：
Kurisaki, JI
中科院分区：
文献类型：
--
作者：
Tsuji, NM;Mizumachi, K;Kurisaki, JI
我们证明了在小鼠Peyer‘s Patches(PPS)中，小剂量的β-乳球蛋白(BLG)喂养后可以诱导出抗原特异性的白介素10(IL-10)分泌细胞。此外，我们还发现PP细胞在体外可以抑制T细胞的增殖反应，在体内也可以抑制T细胞介导的炎症反应。这些调节细胞介导的主动抑制仅在很小的抗原剂量范围内(喂食)出现，在5×1 mg BLG时效果最显著。在这个范围的两侧，当PP细胞在体外被抗原刺激时，观察到T辅助分子1样的细胞因子反应。这一结果与调节性细胞因子的产生减少以及旁观者抑制活动的减少有关。我们发现，IL-10产生的变化与干扰素-伽马产生的变化呈负相关。抗IL-10抗体和转化生长因子-β抗体部分中和了由CD4(+)PP细胞介导的抑制效应。有趣的是，在低剂量BLG喂养后，这种调节细胞的产生表现出器官依赖性。在口服耐受小鼠的脾、淋巴结和PP细胞中，PP细胞在BLG存在下促进旁观者抑制的效果最好，这表明PPS在诱导小剂量口服耐受时是抗原特异性调节细胞的诱导部位。此外，喂养5x1 mg BLG的小鼠的PP细胞被显示出抑制足垫诱导的BLG特异性迟发性超敏反应，这表明分泌IL-10的PP细胞调节全身炎症。
We demonstrate the induction of antigen-specific interleukin-10 (IL-10)-secreting cells in murine Peyer's patches (PPs) after low-dose beta -lactoglobulin (BLG) feeding. In addition, we show that PP cells can inhibit the T-cell proliferative response in vitro as well as T-cell-mediated inflammation in vivo. The active suppression mediated by these regulatory cells was seen only within a narrow range of antigen dosage (feeding), with the most prominent effect at 5 x 1 mg BLG. On either side of this range, T-helper 1-like cytokine responses were observed when PP cells were stimulated with antigen in vitro. This result correlated with reduced production of regulatory cytokines as well as reduced activity of bystander suppression. We found that changes in IL-10 production correlated inversely with changes in interferon-gamma production. Inhibitory effects mediated by CD4(+) PP cells were partially neutralized by antibodies to IL-10 and transforming growth factor-beta. Interestingly, the generation of such regulatory cells after low-dose BLG feeding exhibited organ dependence. Among spleen, lymph node and PP cells derived from orally tolerized mice, PP cells were the most effective in promoting bystander suppression in the presence of BLG, indicating the significance of PPs as an inductive site for antigen-specific regulatory cells upon induction of low-dose oral tolerance. Moreover, PP cells from mice fed 5 x 1 mg BLG were shown to suppress a BLG-specific delayed-type hypersensitivity response induced in footpads, suggesting that IL-10-secreting PP cells regulate systemic inflammation.