Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
J Immunol. 2010 Jan 1;184(1):56-66. doi: 10.4049/jimmunol.0902379. Epub 2009 Nov 30.
The importance of high TCR diversity of T regulatory (Treg) cells for self-tolerance is poorly understood. To address this issue, TCR diversity was measured for Treg cells after transfer into IL-2Rbeta(-/-) mice, which develop lethal autoimmunity because of failed production of Treg cells. In this study, we show that high TCR diversity of pretransferred Treg cells led to selection of therapeutic Treg cells with lower TCR diversity that prevented autoimmunity. Pretransferred Treg cells with lower diversity led to selection of Treg cells through substantial peripheral reshaping with even more restricted TCR diversity that also suppressed autoimmune symptoms. Thus, in a setting of severe breakdown of immune tolerance because of failed production of Treg cells, control of autoimmunity is achieved by only a fraction of the Treg TCR repertoire, but the risk for disease increased. These data support a model in which high Treg TCR diversity is a mechanism to ensure establishing and maintaining self-tolerance.
T 调节（Treg）细胞的 TCR 多样性对于自身耐受的重要性尚未得到充分理解。为了解决这个问题，我们在将 Treg 细胞转移到 IL-2Rβ（-/-）小鼠后测量了 TCR 多样性，这些小鼠由于 Treg 细胞产生失败而发展为致命的自身免疫。在这项研究中，我们表明，预先转移的 Treg 细胞的高 TCR 多样性导致了具有较低 TCR 多样性的治疗性 Treg 细胞的选择，从而预防了自身免疫。具有较低多样性的预先转移的 Treg 细胞通过大量外周重塑导致了甚至更受限制的 TCR 多样性的 Treg 细胞的选择，这也抑制了自身免疫症状。因此，在由于 Treg 细胞产生失败而导致免疫耐受严重破裂的情况下，自身免疫的控制仅通过 Treg TCR 库的一小部分来实现，但疾病的风险增加了。这些数据支持这样一种模型，即高 Treg TCR 多样性是确保建立和维持自身耐受的一种机制。
