Murine ileitis after intracellular parasite infection is controlled by TGF-β-producing intraepithelial lymphocytes
Murine ileitis after intracellular parasite infection is controlled by TGF-β-producing intraepithelial lymphocytes
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DOI：
10.1053/gast.2001.22432a
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发表时间：
2001-03-01
期刊：
影响因子：
29.4
通讯作者：
Kasper, LH
中科院分区：
文献类型：
--
作者：
Buzoni-Gatel, D;Debbabi, H;Kasper, LH
背景与目的：易感(C57BL/6)小鼠口服感染弓形虫后发生急性炎症性回肠炎。干扰素(干扰素)-γ的过度产生和一氧化氮的合成介导了炎症。我们评估了由上皮内淋巴细胞(IEL)产生的转化生长因子(TGF)-β在这一过程中的作用。方法：我们分析了在口服弓形虫包囊前，将抗原致敏的IEL过继转移到经抗转化生长因子-β抗体治疗的易感小鼠体内的组织学和免疫学后果。肠细胞和IEL的体外共培养评估了在存在抗转化生长因子-β的情况下趋化因子和细胞因子的产生。结果：抗原准备的IEL预防了易感小鼠的急性回肠炎，而抗转化生长因子-β则逆转了这一作用。耐药小鼠(CBA/J)经抗转化生长因子-β抗体治疗后发生回肠炎。通过抑制干扰素-γ的产生来衡量，抗原致敏的IEL可以诱导全身免疫抑制。结论：弓形虫回肠炎症过程的调节依赖于转化生长因子-β的产生，IEL是口腔感染后肠道动态平衡的重要组成部分。
Background & Aims:Acute inflammatory ileitis occurs in susceptible (C57BL/6) mice after oral infection with Toxoplasma gondii. Overproduction of interferon (IFN)-gamma and synthesis of nitric oxide mediate the inflammation. We evaluated the role of transforming growth factor (TGF)-beta produced by intraepithelial lymphocytes (IELs) in this process. Methods: We analyzed the histologic and immunologic consequences of adoptive transfer of antigen-primed IELs into susceptible mice treated with anti-TGF-beta before oral challenge with T. gondii cysts. An in vitro coculture of enterocytes and IELs assessed the production of chemokines and cytokines in the presence of anti-TGF-beta, Results: Antigen-primed IELs prevent acute ileitis in susceptible mice that is reversed with anti-TGF-beta. Resistant mice (CBA/J) develop ileitis after treatment with anti-TGF-beta. Antigen-primed IELs can induce systemic immunosuppression as measured by depressed IFN-gamma production. In vitro, primed IELs reduce the production of inflammatory chemokines by infected enterocytes and IFN-gamma by splenocytes, Conclusions: Regulation of the ileal inflammatory process resulting from T, gondii is dependent on TGF-beta -producing IELs, The IELs ape an essential component in gut homeostasis after oral infection with this parasite.