Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses.
Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses.
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DOI：
10.1084/jem.188.12.2277
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发表时间：
1998-12-21
期刊：
影响因子：
--
通讯作者：
Monath TP
中科院分区：
文献类型：
--
作者：
Ermak TH;Giannasca PJ;Nichols R;Myers GA;Nedrud J;Weltzin R;Lee CK;Kleanthous H;Monath TP
我们研究了细胞和抗体介导的免疫在尿素酶疫苗诱导的抗幽门螺杆菌感染保护中的作用。用尿素酶+大肠杆菌不耐热肠毒素（LT）粘膜免疫或用尿素酶+氢氧化铝或糖脂佐剂胃肠外免疫缺乏主要组织相容性复合物（MHC）I类、MHC II类或B细胞应答的正常小鼠和基因敲除小鼠，用H. pylori菌株X47-2AL和H.定量胃粘膜中的幽门螺杆菌和白细胞浸润。在正常小鼠的佐剂/途径研究中，保护水平与招募到胃粘膜的T细胞密度之间存在直接相关性。在基因敲除研究中，用尿素酶加LT口服免疫保护MHC I类基因敲除小鼠[β2-微球蛋白（−/−）]，但不能保护MHC II类基因敲除小鼠[I-Ab（−/−）]。在B细胞敲除小鼠[μMT（−/−）]中，疫苗诱导的保护作用与在免疫野生型（+/+）小鼠中观察到的保护作用相当;在胃中未检测到伊加+细胞，但观察到与野生型（+/+）小鼠相当的CD 4+细胞水平。这些研究表明，保护小鼠免受H。通过用尿素酶抗原免疫的幽门螺杆菌感染依赖于MHC II类限制的细胞介导机制，并且保护不需要对尿素酶的抗体应答。
We examined the roles of cell- and antibody-mediated immunity in urease vaccine–induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [β2-microglobulin (−/−)] but not MHC class II knockout mice [I-Ab (−/−)]. In B cell knockout mice [μMT (−/−)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4+ cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II–restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.