Kunisawa Jun, Takahashi Ichiro, Okudaira Akiko, Hiroi Takachika, Katayama Kazufumi, Ariyama Teruko, Tsutsumi Yasuo, Nakagawa Shinsaku, Kiyono Hiroshi, Mayumi Tadanori
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Eur J Immunol. 2002 Aug;32(8):2347-55. doi: 10.1002/1521-4141(200208)32:8<2347::AID-IMMU2347>3.0.CO;2-V.
Peyer's patches (PP) represent a well-characterized inductive site in gut-associated lymphoid tissue that actively acquires antigens from the intestinal lumen. It was reported that organized PP are not required for antigen-specific IgA responses induced by oral immunization with soluble antigen mixed with the mucosal adjuvant, cholera toxin. However, the role of PP in the induction of mucosal and systemic immune responses remains to be clarified in the case of particulate antigen. Here, we created PP-null mice by treating them with monoclonal anti-IL-7 receptor alpha chain (IL-7 R alpha) antibody during gestation and then immunized with antigen-encapsulated poly-lactic acid (PLA) microspheres. Brisk OVA-specific antibody responses were noted in serum and fecal extracts of normal mice following direct intestinal immunization with OVA in PBS (OVA-PBS) as well as in PLA-microspheres (OVA-MS). Antibody production was similarly elevated in PP-null mice immunized with OVA-PBS via direct injection into the intestinal tract. In contrast, OVA-specific antibody responses were dramatically decreased in both serum and fecal extracts collected from PP-null mice immunized intestinally with OVA-MS. These results were further supported by the number of OVA-specific antibody-forming cells detected in the spleen and intestinal lamina propria. PP deficiency also resulted in the reduction in OVA-specific Th1/Th2 cell responses in the spleen and mesenteric lymph nodes of mice intestinally immunized with OVA-MS. These results suggested that organized PP do, in fact, play a crucial role in the induction of antigen-specific immune responses against ingested particulate antigen.
派尔集合淋巴结(PP)是肠道相关淋巴组织中一个特征明确的诱导部位,可从肠腔中主动摄取抗原。据报道,对于用与粘膜佐剂霍乱毒素混合的可溶性抗原进行口服免疫诱导的抗原特异性IgA反应,有组织的PP并非必需。然而,在颗粒性抗原的情况下,PP在诱导粘膜和全身免疫反应中的作用仍有待阐明。在此,我们通过在妊娠期用抗白细胞介素-7受体α链(IL-7Rα)单克隆抗体处理小鼠来创建PP缺失小鼠,然后用包封抗原的聚乳酸(PLA)微球进行免疫。在用OVA-PBS(OVA溶解于PBS)以及PLA微球(OVA-MS)对正常小鼠进行直接肠道免疫后,在其血清和粪便提取物中观察到了强烈的OVA特异性抗体反应。通过直接注入肠道用OVA-PBS免疫的PP缺失小鼠中,抗体产生同样升高。相比之下,在用OVA-MS进行肠道免疫的PP缺失小鼠收集的血清和粪便提取物中,OVA特异性抗体反应显著降低。在脾脏和肠固有层中检测到的OVA特异性抗体形成细胞数量进一步支持了这些结果。PP缺陷还导致在用OVA-MS进行肠道免疫的小鼠脾脏和肠系膜淋巴结中OVA特异性Th1/Th2细胞反应减少。这些结果表明,有组织的PP实际上在针对摄入的颗粒性抗原诱导抗原特异性免疫反应中起着关键作用。