Istituto di ematologia, Università di Sassari, Sassari, Italy.
Immunobiology. 2012 Sep;217(9):920-5. doi: 10.1016/j.imbio.2012.01.002. Epub 2012 Jan 4.
Several data suggest that stochastic rearrangements of the TCR could play a pathogenic role in both disease predisposition and protection in type 1 diabetes (T1D). As twin sets offer an enormous potential in evaluating the role of genetic and environmental factors in susceptibility to disease, the main goal of this study was to assess whether the degree of sharing of the expressed TCR repertoire of twin pairs discordant for T1D differs from that of disease concordant pairs. We performed our analysis in 5 pairs of monozygotic twins, 3 of which were concordant and 2 discordant for T1D, by combining flow cytometry and CDR3 spectratyping on both CD4+ and CD8+ T-cells. Our data show that TCR repertoires show increased level of concordance within each twin pair, especially in CD8+ cells, in terms of mean BV expression levels on flow cytometry as well as of CDR3 patterns and frequencies of skewed or oligoclonal BV subfamilies on spectratyping. It is worth noting that the degree of similarity among twins seems to be independent of concordance or discordance for T1D. Our findings seem to suggest that in monozygotic twins with T1D the TCR repertoire is influenced by genetic factors more than by the presence of the autoimmune disorder itself.
有几项数据表明，T 细胞受体（TCR）的随机重排可能在 1 型糖尿病（T1D）的疾病易感性和保护中发挥致病作用。由于双胞胎提供了评估遗传和环境因素在疾病易感性中的作用的巨大潜力，本研究的主要目的是评估 T1D 双生子中表达的 TCR 谱的共享程度是否与疾病一致的双生子不同。我们通过结合流式细胞术和 CDR3 谱分析，对 5 对单卵双胞胎（其中 3 对 T1D 一致，2 对不一致）进行了分析，这些双胞胎同时分析了 CD4+和 CD8+ T 细胞。我们的数据表明，TCR 谱在每个双胞胎内显示出更高的一致性水平，特别是在 CD8+细胞中，表现在流式细胞术上的平均 BV 表达水平、CDR3 模式以及偏斜或寡克隆 BV 亚家族的频率。值得注意的是，双胞胎之间的相似程度似乎与 T1D 的一致性或不一致性无关。我们的研究结果似乎表明，在患有 T1D 的同卵双胞胎中，TCR 谱受遗传因素的影响大于自身免疫性疾病的存在。
