CD25+CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production
CD25+CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production
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DOI：
10.1093/intimm/dxh207
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Stockinger, B
中科院分区：
文献类型：
--
作者：
Barthlott, T;Moncrieffe, H;Stockinger, B
维持免疫系统的稳态涉及T淋巴细胞之间的资源竞争，这避免了淋巴细胞减少小鼠中所见的免疫病理学的发展。CD 25（+）CD 4（+）T细胞对体内平衡很重要，但对其作用机制尚未达成共识。尽管在体外共培养系统中，CD 25（+）CD 4（+）T细胞引起应答T细胞中IL-2 mRNA的显著下调，但IL-蛋白的存在可以通过细胞内染色来证明。作为竞争IL-2的结果，CD 25（+）CD 4（+）T细胞进一步上调IL-2 R α链（CD 25），这是一个严格依赖于IL-2的过程，而应答T细胞不能上调CD 25。类似地，过继转移到淋巴细胞减少小鼠中显示，CD 25（+）CD 4（+）T细胞干扰共转移的幼稚T细胞上的CD 25上调，同时增加其自身的CD 25水平。通过CD 25（+）CD 4（+）T细胞的IL-2隔离不是一种被动现象，而是与通过TCR的信号一起启动它们分化为IL-10的产生。虽然IL-10不是体外抑制所必需的，但它对调节性T细胞的体内功能至关重要。我们的数据提供了一个链接，解释在体外和体内的调节机制的明显差异。
Maintenance of homeostasis in the immune system involves competition for resources between T lymphocytes, which avoids the development of immune pathology seen in lymphopenic mice. CD25(+)CD4(+) T cells are important for homeostasis, but there is as yet no consensus on their mechanisms of action. Although CD25(+)CD4(+) T cells cause substantial down-regulation of IL-2 mRNA in responder T cells in an in vitro co-culture system, the presence of IL- protein can be demonstrated by intracellular staining. As a consequence of competition for IL-2, CD25(+)CD4(+) T cells further up-regulate the IL-2R alpha chain (CD25), a process that is strictly dependent on IL-2, whereas responder T cells fail to up-regulate CD25. Similarly, adoptive transfer into lymphopenic mice showed that CD25(+)CD4(+) T cells interfere with CD25 up-regulation on co-transferred naive T cells, while increasing their own CD25 levels. IL-2 sequestration by CD25(+)CD4(+) T cells is not a passive phenomenon but instead initiates-in conjunction with signals through the TCR-their differentiation to IL-10 production. Although IL-10 is not required for in vitro suppression, it is vital for the in vivo function of regulatory T cells. Our data provide a link explaining the apparent difference in regulatory mechanisms in vitro and in vivo.