Demonstration of strong enterobacterial reactivity of CD4+CD25- T cells from conventional and germfree mice which is counter-regulated by CD4+CD25+ T cells
Demonstration of strong enterobacterial reactivity of CD4+CD25- T cells from conventional and germfree mice which is counter-regulated by CD4+CD25+ T cells
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DOI：
10.1002/eji.200324394
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Claesson, MH
中科院分区：
文献类型：
--
作者：
Gad, M;Pedersen, AE;Claesson, MH
来自肠道相关淋巴组织（GALT）和外周淋巴结的未分离CD4(+) T细胞在体外暴露于肠杆菌抗原时无反应。在类似的条件下，体内或体外CD4(+)CD25(+) T细胞的CD4(+) T细胞大量增殖。CD4(+)CD25(-) T细胞的反应性取决于MHC II类递呈、特异性TCR刺激、CD4结扎和抗原递呈细胞的抗原加工。CD4(+)CD25(-) T细胞对自体和异源肠杆菌抗原有应答，但对无菌小鼠粪便中的抗原无应答。令人惊讶的是，从无菌小鼠的GALT中获得的CD4(+)CD25(-) T细胞在暴露于肠杆菌抗原时也会增殖，并且将常规或无菌CD4(+)CD25(+) T细胞添加到肠抗原刺激的CD4(+)CD25(-) T细胞中可以消除增殖。根据羧基荧光素二醋酸琥珀酰亚胺酯标记实验判断，4-5%的CD4(+)CD25(-) T细胞对肠抗原有应答。这些数据首次表明，CD4(+)CD25(-) T细胞对肠杆菌菌群和调节性CD4(+)CD25(+) T细胞具有反应性，在常规和无菌小鼠中都存在。这些数据表明，很大一部分外周CD4(+)CD25(-) T细胞库表达抗肠杆菌反应性，由于调节性CD4(+)CD25(+) T细胞的存在，这种反应性保持在静止状态。
Unfractionated CD4(+) T cells from the gut-associated lymphoid tissue (GALT) and peripheral lymph nodes are unresponsive when exposed to enterobacterial antigens in vitro. Under similar conditions, CD4(+) T cells depleted in vivo or in vitro of CD4(+)CD25(+) T cells proliferate extensively. The CD4(+)CD25(-) T cell reactivity depends on MHC class II presentation, specific TCR stimulation, CD4 ligation, and antigen processing by antigen-presenting cells. The CD4(+)CD25(-) T cells respond to autologous and heterologous enterobacterial antigens, but not to antigens from the feces of germ-free mice. Surprisingly, CD4(+)CD25(-) T cells obtained from the GALT of germ-free mice also proliferate when exposed to enterobacterial antigens, and adding back the conventional or germ-free CD4(+)CD25(+) T cells to the enteroantigenstimulated CD4(+)CD25(-) T cells abolishes proliferation. As judged from carboxyfluorescein diacetate succinimidyl ester-labeling experiments, 4-5% of the CD4(+)CD25(-) T cells respond to enteroantigen. The data show for the first time that CD4(+)CD25(-) T cells with reactivity towards the enterobacterial flora and regulatory CD4(+)CD25(+) T cells are present in both conventional and germ-free mice. The data suggest that a significant proportion of the peripheral pool of CD4(+)CD25(-) T cells express anti-enterobacterial reactivity, which, due to the presence of regulatory CD4(+)CD25(+) T cells, is kept in a quiescent state.