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白细胞介素-10基因敲除小鼠中幽门螺杆菌感染的减少依赖于CD4 + T细胞,而非肥大细胞。

Reduction of Helicobacter infection in IL-10-/- mice is dependent on CD4+ T cells but not on mast cells.

作者信息

Velin Dominique, Bachmann Daniel, Bouzourene Hanifa, Michetti Pierre

机构信息

Service de Gastro-entérologie et d'Hépatologie, Centre Hospitalier Uniersitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

出版信息

Helicobacter. 2008 Oct;13(5):361-9. doi: 10.1111/j.1523-5378.2008.00614.x.

Abstract

BACKGROUND

In contrast to wild type, interleukin-10-deficient (IL-10(-/-)) mice are able to clear Helicobacter infection. In this study, we investigated the immune response of IL-10(-/-) mice leading to the reduction of Helicobacter infection.

MATERIALS AND METHODS

We characterized the immune responses of Helicobacter felis-infected IL-10(-/-) mice by studying the systemic antibody and cellular responses toward Helicobacter. We investigated the role of CD4(+) T cells in the Helicobacter clearance by injecting H. felis-infected IL-10(-/-) mice with anti-CD4 depleting antibodies. To examine the role of mast cells in Helicobacter clearance, we constructed and infected mast cells and IL-10 double-deficient mice.

RESULTS

Reduction of Helicobacter infection in IL-10(-/-) mice is associated with strong humoral (fivefold higher serum antiurease antibody titers were measured in IL-10(-/-) in comparison to wild-type mice, p < .008) and cellular (urease-stimulated splenic CD4(+) T cells isolated from infected IL-10(-/-) mice produce 150-fold more interferon-gamma in comparison to wild-type counterparts, p < .008) immune responses directed toward Helicobacter. Depletion of CD4(+) cells from Helicobacter-infected IL-10(-/-) mice lead to the loss of bacterial clearance (rapid urease tests are threefold higher in CD4(+) depleted IL-10(-/-) in comparison to nondepleted IL-10(-/-) mice, p < .02). Mast cell IL-10(-/-) double-deficient mice clear H. felis infection, indicating that mast cells are unnecessary for the bacterial eradication in IL-10(-/-) mice.

CONCLUSION

Taken together, these results suggest that CD4(+) cells are required for Helicobacter clearance in IL-10(-/-) mice. This reduction of Helicobacter infection is, however, not dependent on the mast cell population.

摘要

背景

与野生型小鼠相比,白细胞介素-10缺陷(IL-10(-/-))小鼠能够清除幽门螺杆菌感染。在本研究中,我们调查了导致IL-10(-/-)小鼠幽门螺杆菌感染减少的免疫反应。

材料与方法

我们通过研究针对幽门螺杆菌的全身抗体和细胞反应,对感染了幽门螺杆菌的IL-10(-/-)小鼠的免疫反应进行了特征描述。我们通过给感染了幽门螺杆菌的IL-10(-/-)小鼠注射抗CD4耗竭抗体,研究了CD4(+) T细胞在幽门螺杆菌清除中的作用。为了研究肥大细胞在幽门螺杆菌清除中的作用,我们构建并感染了肥大细胞和IL-10双缺陷小鼠。

结果

IL-10(-/-)小鼠中幽门螺杆菌感染的减少与针对幽门螺杆菌的强烈体液免疫(与野生型小鼠相比,IL-10(-/-)小鼠血清抗脲酶抗体滴度高五倍,p < 0.008)和细胞免疫(从感染的IL-10(-/-)小鼠中分离出的脲酶刺激的脾CD4(+) T细胞产生的干扰素-γ比野生型对应细胞多150倍,p < 0.008)反应相关。从感染幽门螺杆菌的IL-10(-/-)小鼠中耗尽CD4(+)细胞导致细菌清除能力丧失(与未耗尽的IL-10(-/-)小鼠相比,CD4(+)耗尽的IL-10(-/-)小鼠的快速脲酶试验高3倍,p < 0.02)。肥大细胞IL-10(-/-)双缺陷小鼠清除了幽门螺杆菌感染,表明肥大细胞对于IL-10(-/-)小鼠中的细菌根除不是必需的。

结论

综上所述,这些结果表明CD4(+)细胞是IL-10(-/-)小鼠清除幽门螺杆菌所必需的。然而,这种幽门螺杆菌感染的减少并不依赖于肥大细胞群体。

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