Differential stimulation of interleukin-12, (IL-12) and IL-10 by live and killed Helicobacter pylori in vitro and association of IL-12 production with gamma interferon-producing T cells in the human gastric mucosa

Differential stimulation of interleukin-12, (IL-12) and IL-10 by live and killed Helicobacter pylori in vitro and association of IL-12 production with gamma interferon-producing T cells in the human gastric mucosa
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DOI:
10.1128/iai.65.10.4229-4235.1997
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发表时间:
1997-10-01
影响因子:
3.1
通讯作者:
Ernst, PB
Ernst, PB
中科院分区:
医学2区
文献类型:
--
作者:
Haeberle, HA;Kubin, M;Ernst, PB

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这些实验的目的是检测幽门螺杆菌刺激白介素10(IL-10)或IL-12的能力,并选择Th1或Th2细胞。胃活检标本来自根据幽门螺杆菌和胃病的存在以及他们的年龄、性别、药物和其他因素进行分类的患者。由于Th1和Th2细胞分别由IL-12和IL-10选择,因此对活检标本进行了这些细胞因子的mRNA和蛋白筛选。虽然在感染和未感染患者的活检标本中都检测到IL-12和IL-IO的mRNA,但IL-12蛋白占主导地位。感染后胃组织中IL-10和IL-12水平无明显变化。此外,在感染和未感染的胃粘膜中都发现了产生干扰素(TFN-γ)的T细胞。用不同浓度的活或灭活幽门螺杆菌刺激感染或未感染的供者外周血白细胞,可诱导免疫反应IL-12和IL-IO。经活幽门螺杆菌刺激后,IL-12水平增加了30多倍,而IL-10水平只增加了2-5倍,与单独使用培养基刺激的细胞相比。有趣的是,灭活的幽门螺杆菌比活的幽门螺杆菌产生更多的IL-10(P<0.05),而重组尿素酶只诱导IL-10;这些结果表明,活的幽门螺杆菌选择性地刺激产生干扰素-γ的IL-12和THL细胞的诱导,而用于口服疫苗的制剂诱导更多的IL-10,并可能有利于Th2细胞的反应。
The objective of these experiments was to examine the ability of Helicobacter pylori to stimulate interleukin-10 (IL-10) or IL-12 and select for either Th1 or Th2 cells. Gastric biopsy specimens were collected from patients who were categorized with respect to the presence of H. pylori and gastric disease as well as their age, gender, medications, and other factors. As Thl and Th2 cells are selected by IL-12 and IL-10, respectively, biopsy specimens were screened for mRNA and protein for these cytokines. Although mRNA for IL-12 and IL-IO was detected in biopsy specimens obtained from both infected and uninfected patients, IL-12 protein predominated. Levels of IL-10 and IL-12 in gastric tissue did not change in response to infection. Moreover, gamma interferon (TFN-gamma)-producing T cells were found in both the infected and the uninfected gastric mucosa. Stimulation of peripheral blood leukocytes from either infected or uninfected donors with various concentrations of live or killed H. pylori induced immunoreactive IL-12 and IL-IO. After stimulation with live H. pylori,; IL-12 levels increased more than 30-fold, whereas IL-10 levels increased only 2- to 5-fold, compared to cells stimulated with medium alone. Interestingly, killed H. pylori induced Significantly more IL-10 (P < 0.05) than live H. pylori, while recombinant urease only induced IL-10; These results demonstrate that live H. pylori selectively stimulates the induction of IL-12 and Thl cells that produce IFN-gamma, whereas preparations used in oral vaccines induce more IL-10 and may favor Th2 cell responses.