Ontogeny and localization of the cells produce IL-2 in healthy animals
Ontogeny and localization of the cells produce IL-2 in healthy animals
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DOI：
10.1016/j.cyto.2012.11.026
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发表时间：
2013-03-01
期刊：
影响因子：
3.8
通讯作者：
Iwashima, Makio
中科院分区：
文献类型：
--
作者：
Yamamoto, Mutsumi;Seki, Yoichi;Iwashima, Makio
IL-2是活化的T细胞的生长因子，并且是维持天然产生的调节性T细胞（nT细胞）所必需的。IL-2/IL-2受体信号传导途径缺陷的小鼠具有受损的nT细胞，并患有淋巴组织增生性疾病，这表明IL-2在健康动物中存在并起作用。然而，IL-2的细胞来源目前尚不清楚。为了确定哪些细胞在健康动物中产生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-2（cre））。当IL-2（cre）小鼠与EGFP报告小鼠杂交时，EGFP仅由淋巴和非淋巴组织中存在的一部分CD 4 T细胞表达。携带荧光素酶报告基因的IL-2（cre）小鼠的实时成像显示荧光素酶（+）细胞集中定位在派伊尔集合淋巴结中。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，表明环境抗原的识别对于在健康动物中产生这些IL-2生产者是必要的。EGFP（+）细胞的相当大部分也产生IL-10和IFN-γ，这是1型调节性T细胞（Tr 1）的特征。这些数据表明，一组Tr 1细胞通过产生IL-2沿着其他细胞因子在免疫稳态中具有额外的作用，并有助于维持TcR。(C)2012爱思唯尔有限公司保留所有权利。
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-2(cre)). When IL-2(cre) 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-2(cre) 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 3 days 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-gamma, 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. (C) 2012 Elsevier Ltd. All rights reserved.