Elliott J I, Altmann D M
Section of Transplantation Biology, R.P.M.S. Hammersmith Hospital, London, GB.
Eur J Immunol. 1996 Apr;26(4):953-6. doi: 10.1002/eji.1830260436.
To test the hypothesis that T cells carrying two T cell receptor (TCR) alpha chains play a role in autoimmunity, we backcrossed the non-obese diabetic (NOD) strain with one carrying a TCR alpha gene disrupted by homologous recombination. Mice carrying one copy of the disrupted gene are incapable of generating T cells carrying two cell surface TCR alpha chains. Our early results suggested that either dual TCR alpha T cells play a role in insulin-dependent diabetes mellitus (IDDM) induction in NOD mice or that a locus co-segregating with the disrupted TCR alpha locus protected mice from diabetes induction. From the analysis both of mice in which the region co-segregating with the disrupted TCR alpha locus is minimized and of the F1 offspring of NOD mice with the 129 strain (TCR alpha hemizygous mice), the apparent protective effect of the absence of dual TCR alpha T cells is lost; thus, such cells do not appear to play a critical role in autoimmune disease in NOD mice.
为了验证携带两条T细胞受体（TCR）α链的T细胞在自身免疫中发挥作用这一假说，我们将非肥胖糖尿病（NOD）品系与携带通过同源重组破坏的TCRα基因的品系进行了回交。携带一个 disrupted 基因拷贝的小鼠无法产生携带两条细胞表面TCRα链的T细胞。我们早期的结果表明，要么双TCRα T细胞在NOD小鼠的胰岛素依赖型糖尿病（IDDM）诱导中起作用，要么与破坏的TCRα基因座共分离的一个基因座保护小鼠免受糖尿病诱导。通过对与破坏的TCRα基因座共分离区域最小化的小鼠以及NOD小鼠与129品系（TCRα半合子小鼠）的F1后代的分析，缺乏双TCRα T细胞的明显保护作用消失了；因此，这类细胞似乎在NOD小鼠的自身免疫疾病中不发挥关键作用。
