Induction of mucosal tolerance in Peyer's patch-deficient, ligated small bowel loops
Induction of mucosal tolerance in Peyer's patch-deficient, ligated small bowel loops
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DOI：
10.1172/jci19102
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发表时间：
2005-08-01
影响因子：
15.9
通讯作者：
Mayer, L
中科院分区：
文献类型：
--
作者：
Kraus, TA;Brimnes, J;Mayer, L
为了探讨M细胞和Peyer‘s补片(PP)在诱导口服耐受中的需求，并探讨肠上皮细胞作为非专业性APC在体内的潜在作用，我们尝试在没有M细胞和Peyer’s补片的结扎小鼠的小肠环上诱导耐受。在没有破坏肠系膜连接的情况下，将一段2厘米长的带血管的小肠从肠道中拼接出来。在脚垫免疫前，我们直接将卵清蛋白引入管腔。通过切除一些小鼠含有PPS的肠段和另一些没有补片的肠段，我们可以研究M细胞和潜在的补片与上皮细胞在诱导粘膜耐受中的必要性。我们发现，无论是在含有PP的环中还是在没有补丁的环中，先前给予OVA的小鼠的OVA特异性T细胞增殖和血清抗体反应都降低了。此外，在没有PPS的情况下，可以诱导高剂量和低剂量的耐受。低剂量耐受与旁观者抑制有关，需要IL-10，这表明主动抑制和调节细胞的诱导。这些数据表明，除PPS外，粘膜免疫系统的组成部分在抗原采样和诱导口服耐受中起着关键作用。
To explore the requirement for M cells and the Peyer's patch (PP) in induction of oral tolerance and address the potential in vivo role of intestinal epithelial cells as nonprofessional APCs, we have attempted to induce tolerance in mice with ligated small bowel loops without M cells and Peyer's patches. A 2-centimeter section of vascularized small bowel was spliced away from the gut without disruption of the mesenteric attachments. We introduced OVA directly into the lumen of the loop prior to footpad immunization. By excising segments of bowel that contain PPs in some mice and segments without patches in others, we could study the necessity of the M cell and the underlying patch versus epithelial cells in induction of mucosal tolerance. We show that OVA-specific T cell proliferation and serum antibody responses are reduced in mice that have previously been given OVA both in PP-containing loops and in loops without patches. Furthermore, both high- and low-dose tolerance could be induced in the absence of PPs. Low-dose tolerance is associated with bystander suppression and requires IL-10, which indicates active suppression and the induction of regulatory cells. These data suggest that there is a critical role for components of the mucosal immune system other than PPs in antigen sampling and induction of oral tolerance.