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Ontogeny and localization of the cells produce IL-2 in healthy animals

机译:细胞的个体发育和定位在健康动物中产生IL-2

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IL-2 is a growth factor for activated T cells and is required for maintenance of naturally arising regulatory T cells (nTregs). Mice defective in IL-2/IL-2 receptor signaling pathways have impaired nTregs and suffer from lymphoproliferative disorders, suggesting that IL-2 is present and functional in healthy animals. However, the cellular source of IL-2 is currently unknown. To determine which cells produce IL-2 in healthy animals, we established mice carrying cre gene knock in at the il-2 locus (termed IL-2cre). When IL-2cre mice were crossed with EGFP reporter mice, EGFP was exclusively expressed by a fraction of CD4 T cells present in both lymphoid and non-lymphoid tissues. Live imaging of IL-2cre mice that carry the luciferase reporter showed concentrated localization of luciferase+ cells in Peyer's patches. These cells were not observed in new born mice but appeared within 3days after birth. Reduction of antigen receptor repertoire by transgene expression reduced their number, indicating that recognition of environmental antigens is necessary for generation of these IL-2 producers in healthy animals. A substantial fraction of EGFP+ cells also produce IL-10 and IFN-??, a characteristic profile of type 1 regulatory T cells (Tr1). The data suggest that a group of Tr1 cells have addition roles in immune homeostasis by producing IL-2 along with other cytokines and help maintaining Tregs. ? 2012 Elsevier Ltd.
机译:IL-2是活化T细胞的生长因子,是维持天然产生的调节性T细胞(nTreg)所必需的。 IL-2 / IL-2受体信号通路有缺陷的小鼠的nTreg受损,并患有淋巴增生性疾病,这表明IL-2存在于健康动物中并起作用。但是,目前尚不知道IL-2的细胞来源。为了确定健康动物中哪些细胞产生IL-2,我们建立了在il-2位点携带cre基因敲入的小鼠(称为IL-2cre)。当IL-2cre小鼠与EGFP报告基因小鼠杂交时,淋巴和非淋巴组织中都存在的一部分CD4 T细胞专门表达EGFP。携带荧光素酶报道分子的IL-2cre小鼠的实时成像显示,荧光素酶+细胞在Peyer斑块中集中定位。这些细胞在新生小鼠中未观察到,但在出生后3天内出现。通过转基因表达减少抗原受体库减少了它们的数量,这表明环境抗原的识别对于在健康动物中产生这些IL-2生产者是必需的。很大一部分的EGFP +细胞也产生IL-10和IFN-α,这是1型调节性T细胞(Tr1)的特征。数据表明,一组Tr1细胞通过与其他细胞因子一起产生IL-2并帮助维持Treg,在免疫稳态中具有附加作用。 ? 2012爱思唯尔有限公司

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