Accumulation of gammadelta T cells in the lungs and their regulatory roles in Th1 response and host defense against pulmonary infection with Cryptococcus neoformans.
Accumulation of gammadelta T cells in the lungs and their regulatory roles in Th1 response and host defense against pulmonary infection with Cryptococcus neoformans.
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发表时间：
2004
影响因子：
4.4
通讯作者：
K. Uezu;K. Kawakami;K. Miyagi;Y. Kinjo;T. Kinjo;H. Ishikawa;A. Saito
中科院分区：
文献类型：
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作者：
K. Uezu;K. Kawakami;K. Miyagi;Y. Kinjo;T. Kinjo;H. Ishikawa;A. Saito
本研究旨在阐明γ δ T细胞在宿主防御肺部新隐球菌感染中的作用。肺部γ - T细胞在气管内感染后第1天开始增加，第3天或第6天达到峰值，第10天开始下降。单核细胞趋化蛋白(MCP)-1缺陷小鼠中这些细胞的增加与MCP -1缺陷小鼠相似，但NK和NKT细胞的增加明显减少。与对照组IgG处理的小鼠相比，特异性mAb处理的γ δ T细胞小鼠在第14天和第21天肺部活微生物数量显著减少。同样，与对照组小鼠相比，γ δ T细胞缺陷（tcr - δ(-/-)）小鼠中这种真菌病原体的消除也得到了促进。最后，感染后第7天、第14天和第7天，tcr - δ(-/-)小鼠的肺和血清中ifn - γ的水平分别显著高于同窝小鼠，而tgf - β的水平则相反。IL-4和IL-10在这些小鼠之间没有差异。受感染的tcr - δ(-/-)小鼠在再受隐球菌Ags刺激后通过引流淋巴结细胞产生的ifn - γ显著高于对照组小鼠。我们的研究结果表明，在隐球菌感染后，γ δ T细胞以不同于NK和NKT细胞的方式在肺部积聚，并在Th1反应和宿主对这种真菌病原体的抗性的发展中发挥下调作用。
The present study was designed to elucidate the role of gammadelta T cells in the host defense against pulmonary infection with Cryptococcus neoformans. The gammadelta T cells in lungs commenced to increase on day 1, reached a peak level on day 3 or 6, and then decreased on day 10 after intratracheal infection. The increase of these cells was similar in monocyte chemoattractant protein (MCP)-1-deficient mice, although that of NK and NKT cells was significantly reduced. The number of live microorganisms in lungs on days 14 and 21 was significantly reduced in mice depleted of gammadelta T cells by a specific mAb compared with mice treated with control IgG. Similarly, elimination of this fungal pathogen was promoted in gammadelta T cell-deficient (TCR-delta(-/-)) mice compared with control littermate mice. Finally, lung and serum levels of IFN-gamma on days 7 and 14 and on day 7 postinfection, respectively, were significantly higher in TCR-delta(-/-) mice than in littermate mice, whereas levels of TGF-beta showed the opposite results. IL-4 and IL-10 were not different between these mice. IFN-gamma production by draining lymph node cells upon restimulation with cryptococcal Ags was significantly higher in the infected TCR-delta(-/-) mice than in control mice. Our results demonstrated that gammadelta T cells accumulated in the lungs in a manner different from NK and NKT cells after cryptococcal infection and played a down-modulatory role in the development of Th1 response and host resistance against this fungal pathogen.