NKT cells are critical for the initiation of an inflammatory bowel response against Toxoplasma gondii
NKT cells are critical for the initiation of an inflammatory bowel response against Toxoplasma gondii
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DOI：
10.4049/jimmunol.175.2.899
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Buzoni-Gatel, D
中科院分区：
文献类型：
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作者：
Ronet, C;Darche, S;Buzoni-Gatel, D
我们在这项研究中证明了NKT细胞在弓形虫感染C57 BL/6小鼠后诱导的致死性回肠炎中的关键作用。这种肠道炎症是由固有层中IFN-γ的过度产生引起的。通过观察到NKT细胞缺陷小鼠（j α 281（-/-））比C57 BL/6小鼠对致死性回肠炎的发展更具抗性，证实了NKT细胞的意义。j α 281（-/-）小鼠在感染后早期未能在肠中过表达IFN-γ。NKT细胞的这种有害作用通过用α-半乳糖神经酰胺处理而被阻断，其防止C57 BL/6小鼠死亡，但不防止j α 281（-/-）小鼠死亡。这种保护作用的特征在于NKT细胞产生的细胞因子向Th 2型转变，并与肠系膜Foxp 3淋巴细胞数量增加相关。使用其中仅NKT细胞缺乏IL-10基因的嵌合小鼠和用抗CD 25 mAb处理的小鼠，我们鉴定了调节性T细胞作为表现α-半乳糖神经酰胺处理的保护作用所需的IL-10的来源。我们的研究结果强调了NKT细胞参与寄生虫清除，通过将细胞因子谱向Th 1模式转移，同时当Th 1免疫应答仍然不受控制时，转移到免疫病理学表现。
We demonstrated in this study the critical role of NKT cells in the lethal ileitis induced in C57BL/6 mice after infection with Toxoplasma gondii. This intestinal inflammation is caused by overproduction of IFN-gamma in the lamina propria. The implication of NKT cells was confirmed by the observation that NKT cell-deficient mice (j alpha 281(-/-)) are more resistant than C57BL/6 mice to the development of lethal ileitis. j alpha 281(-/-) mice failed to overexpress IFN-gamma in the intestine early after infection. This detrimental effect of NKT cells is blocked by treatment with a-galactosylceramide, which prevents death in C57BL/6, but not in j alpha 281(-/-), mice. This protective effect is characterized by a shift in cytokine production by NKT cells toward a Th2 profile and correlates with an increased number of mesenteric Foxp3 lymphocytes. Using chimeric mice in which only NKT cells are deficient in the IL-10 gene and mice treated with anti-CD25 mAb, we identified regulatory T cells as the source of the IL-10 required for manifestation of the protective effect of a-galactosylceramide treatment. Our results highlight the participation of NKT cells in the parasite clearance by shifting the cytokine profile toward a Th1 pattern and simultaneously to immunopathological manifestation when this Thl immune response remains uncontrolled.