Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4+ Foxp3+ regulatory T cells
Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4+ Foxp3+ regulatory T cells
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DOI：
10.1111/imm.12602
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发表时间：
2016-06-01
期刊：
影响因子：
6.4
通讯作者：
Hansen, Wiebke
中科院分区：
文献类型：
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作者：
Abel, Simone;Ueffing, Kristina;Hansen, Wiebke
最近，我们证明了约氏疟原虫感染小鼠中CD 4（+）Foxp 3（+）调节性T（Treg）细胞数量的增加有助于调节抗疟疾免疫应答。然而，尚不清楚Treg细胞的这种增加是由于胸腺衍生的Treg细胞扩增还是外周中Treg细胞的诱导。在此，我们发现在约氏疟原虫感染的早期时间点，表达神经纤毛蛋白-1（Nrp-1）的Foxp 3（+）Treg细胞的频率降低，而Helios（+）Foxp 3（+）Treg细胞的百分比保持不变。来自约氏疟原虫感染小鼠的Foxp 3（+）Nrp-1（+）和Foxp 3（+）Nrp-1（-）Treg细胞在foxp 3基因座内Treg特异性去甲基化区域中表现出相似的T细胞受体V β链使用和甲基化模式。引人注目的是，我们没有观察到过继转移到约氏疟原虫感染小鼠的Foxp 3（-）T细胞中Foxp 3表达的诱导。因此，我们的结果表明约氏疟原虫感染引发了天然存在的Treg细胞的扩增，而不是Foxp 3（+）Treg细胞的从头诱导。
Recently, we demonstrated elevated numbers of CD4(+) Foxp3(+) regulatory T (Treg) cells in Plasmodium yoelii-infected mice contributing to the regulation of anti-malarial immune response. However, it remains unclear whether this increase in Treg cells is due to thymus-derived Treg cell expansion or induction of Treg cells in the periphery. Here, we show that the frequency of Foxp3(+) Treg cells expressing neuropilin-1 (Nrp-1) decreased at early time-points during P. yoelii infection, whereas percentages of Helios(+) Foxp3(+) Treg cells remained unchanged. Both Foxp3(+) Nrp-1(+) and Foxp3(+) Nrp-1(-) Treg cells from P. yoelii-infected mice exhibited a similar T-cell receptor V beta chain usage and methylation pattern in the Treg-specific demethylation region within the foxp3 locus. Strikingly, we did not observe induction of Foxp3 expression in Foxp3(-) T cells adoptively transferred to P. yoelii-infected mice. Hence, our results suggest that P. yoelii infection triggered expansion of naturally occurring Treg cells rather than de novo induction of Foxp3(+) Treg cells.