Sub-optimal CD4+ T-cell activation triggers autonomous TGF-β-dependent conversion to Foxp3+ regulatory T cells
Sub-optimal CD4+ T-cell activation triggers autonomous TGF-β-dependent conversion to Foxp3+ regulatory T cells
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DOI：
10.1002/eji.201040896
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发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Graca, Luis
中科院分区：
文献类型：
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作者：
Oliveira, Vanessa G.;Caridade, Marta;Graca, Luis
经典的体外Treg转化试验依赖于外源性转化生长因子-β对T细胞的最佳激活，其诱导Foxp3表达的频率远远高于口服或移植耐受Treg依赖模型中体内观察到的频率。我们发现，在没有外源性转化生长因子-β的情况下，在体外，次佳的小鼠T细胞激活导致Foxp3表达的诱导，其频率与我们在体内发现的抗CD4诱导的移植耐受的频率相似。我们发现，低剂量抗CD3或低剂量激动肽触发TCR，以及非耗竭抗CD4下调TCR信号，促进T细胞产生转化生长因子-β，这一事件先于Foxp3表达，并且不依赖于Foxp3。这些发现支持这样的观点，即亚免疫原性疗法导致显性耐受是T细胞固有特性的结果。
Classical in vitro Treg conversion assays, which rely on optimal T-cell activation in the presence of exogenous TGF-beta, induce Foxp3 expression at a frequency far above that which is observed in vivo in Treg-dependent models of oral or transplantation tolerance. We have found that suboptimal murine T-cell activation in vitro results in induction of Foxp3 expression, in the absence of exogenous TGF-beta, at a frequency similar to that which we found in vivo upon anti-CD4-induced transplantation tolerance. We show that TCR triggering with either low-dose anti-CD3 or low-dose agonist peptide, as well as down-modulation of the TCR signal with non-depleting anti-CD4, promotes TGF-beta production by T cells, an event that precedes Foxp3 expression and is Foxp3 independent. These findings support the view that sub-immunogenic regimens lead to dominant tolerance as a result of T-cell intrinsic properties.