Department of Paediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Immunology. 2013 Jul;139(3):309-17. doi: 10.1111/imm.12067.
We identified CD8(+) CD122(+) regulatory T cells (CD8(+) CD122(+) Treg cells) and reported their importance in maintaining immune homeostasis. The absence of CD8(+) CD122(+) Treg cells has been shown to lead to severe systemic autoimmunity in several mouse models, including inflammatory bowel diseases and experimental autoimmune encephalomyelitis. The T-cell receptors (TCRs) expressed on CD8(+) CD122(+) Treg cells recognize the target cells to be regulated. To aid in the identification of the target antigen(s) recognized by TCRs of CD8(+) CD122(+) Treg cells, we compared the TCR diversity of CD8(+) CD122(+) T cells with that of conventional, naive T cells in mice. We analysed the use of TCR-Vβ in the interleukin 10-producing population of CD8(+) CD122(+) T cells marked by high levels of CD49d expression, and found the significantly increased use of Vβ13 in these cells. Immunoscope analysis of the complementarity-determining region 3 (CDR3) of the TCR β-chain revealed remarkable skewing in a pair of Vβ regions, suggesting the existence of clonally expanded cells in CD8(+) CD122(+) T cells. Clonal expansion in Vβ13(+) cells was confirmed by determining the DNA sequences of the CDR3s. The characteristic TCR found in this study is an important building block for further studies to identify the target antigen recognized by CD8(+) CD122(+) Treg cells.
我们鉴定了 CD8(+)CD122(+)调节性 T 细胞（CD8(+)CD122(+)Treg 细胞），并报道了它们在维持免疫稳态中的重要性。在几种小鼠模型中，包括炎症性肠病和实验性自身免疫性脑脊髓炎，缺失 CD8(+)CD122(+)Treg 细胞会导致严重的全身性自身免疫。CD8(+)CD122(+)Treg 细胞表达的 T 细胞受体（TCRs）识别要调节的靶细胞。为了帮助鉴定 CD8(+)CD122(+)Treg 细胞的 TCR 识别的靶抗原（s），我们比较了 CD8(+)CD122(+)T 细胞和常规、幼稚 T 细胞的 TCR 多样性。我们分析了在高水平 CD49d 表达标记的 CD8(+)CD122(+)T 细胞中产生白细胞介素 10 的群体中，TCR-Vβ 的使用情况，并发现这些细胞中 Vβ13 的使用显著增加。TCR β 链的互补决定区 3（CDR3）的 Immunoscope 分析显示，在一对 Vβ 区存在显著的偏斜，表明 CD8(+)CD122(+)T 细胞中存在克隆扩增的细胞。通过确定 CDR3 的 DNA 序列证实了 Vβ13(+)细胞中的克隆扩增。在这项研究中发现的特征性 TCR 是进一步研究鉴定 CD8(+)CD122(+)Treg 细胞识别的靶抗原的重要构建块。
