Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
J Immunol. 2012 Feb 1;188(3):1083-90. doi: 10.4049/jimmunol.1101974. Epub 2011 Dec 21.
Circulating human CD4(+)CD25(++)CD127(-)FOXP3(+) T cells with a persistent demethylated regulatory T cell (Treg)-specific demethylated region Foxp3 gene are considered natural Tregs (nTregs). We have shown that it is possible to identify functional Ag-reactive nTregs cells for a range of different common viral and vaccination Ags. The frequency of these Ag-reactive nTregs within the nTreg population is strikingly similar to the frequency of Ag-reactive T effector cells within the CD4(+) T cell population. The Ag-reactive nTregs could be recognized with great specificity by induction of CD154 expression. These CD154(+) Ag-reactive nTregs showed a memory phenotype and shared all phenotypical and functional characteristics of nTregs. The isolated CD154(+) nTregs could be most efficiently expanded by specific antigenic stimulation, while their Ag-reactive suppressive activity was maintained. After an in vivo booster Ag challenge, the ratio of Ag-reactive T cells to Ag-reactive Tregs increased substantially, which could be attributed to the rise in effector T cells but not Tregs. In conclusion, the nTreg population mirrors the effector T cell population in the frequency of Ag-reactive T cells. Isolation and expansion of functional Ag-reactive nTregs is possible and of potential benefit for specific therapeutic goals.
循环中的人 CD4(+)CD25(++)CD127(-)FOXP3(+)T 细胞具有持续去甲基化的调节性 T 细胞 (Treg)-特异性去甲基化区域 Foxp3 基因，被认为是天然 Tregs(nTregs)。我们已经表明，可以针对一系列不同的常见病毒和疫苗抗原来鉴定具有功能的抗原反应性 nTregs 细胞。这些抗原反应性 nTregs 在 nTreg 群体中的频率与 CD4(+)T 细胞群体中抗原反应性 T 效应细胞的频率非常相似。抗原反应性 nTregs 可以通过诱导 CD154 表达来特异性识别。这些 CD154(+)抗原反应性 nTregs 表现出记忆表型，并具有 nTregs 的所有表型和功能特征。通过特异性抗原刺激，可以最有效地扩增分离的 CD154(+)nTregs，同时保持其抗原反应性的抑制活性。在体内增强抗原挑战后，抗原反应性 T 细胞与抗原反应性 Tregs 的比例显著增加，这可归因于效应 T 细胞的增加而不是 Tregs。总之，nTreg 群体在抗原反应性 T 细胞的频率上反映了效应 T 细胞群体。分离和扩增功能性抗原反应性 nTregs 是可能的，并具有针对特定治疗目标的潜在益处。
