Tong Yin, Li Zhoufang, Zhang Hua, Xia Ligang, Zhang Meng, Xu Ying, Wang Zhanhui, Deem Michael W, Sun Xiaojuan, He Jiankui
Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Genomics Proteomics Bioinformatics. 2016 Dec;14(6):338-348. doi: 10.1016/j.gpb.2016.10.003. Epub 2016 Dec 24.
Type 1 diabetes mellitus (T1D) is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors (TCRs), we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes (T2D) patients, and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients (P=7.0E-08 for CD4 T cells, P=1.4E-04 for CD8 T cells) and nondiabetic controls (P=2.7E-09 for CD4 T cells, P=7.6E-06 for CD8 T cells). Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients (P=5.2E-06 for CD4 T cells, P=1.9E-07 for CD8 T cells) and nondiabetic controls (P=1.7E-07 for CD4 T cells, P=3.3E-03 for CD8 T cells). Furthermore, we identified a group of highly-expanded T cell receptor clones that are shared by more than two T1D patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.
1型糖尿病（T1D）是一种免疫介导的疾病。T1D患者中的自身反应性T细胞会攻击并破坏自身的胰腺细胞。为了系统地研究潜在的自身反应性T细胞受体（TCR），我们使用了高通量免疫组库测序技术来分析个体T1D患者和对照中TCR的谱型。我们对9名T1D患者、4名2型糖尿病（T2D）患者和6名非糖尿病对照的T细胞组库进行了测序。与T2D患者相比，T1D患者T细胞组库的多样性显著降低（CD4 T细胞P = 7.0×10⁻⁸，CD8 T细胞P = 1.4×10⁻⁴），与非糖尿病对照相比也显著降低（CD4 T细胞P = 2.7×10⁻⁹，CD8 T细胞P = 7.6×10⁻⁶）。此外，T1D患者高度扩增的T细胞克隆比T2D患者（CD4 T细胞P = 5.2×10⁻⁶，CD8 T细胞P = 1.9×10⁻⁷）和非糖尿病对照（CD4 T细胞P = 1.7×10⁻⁷，CD8 T细胞P = 3.3×10⁻³）显著更多。此外，我们鉴定出一组由两名以上T1D患者共享的高度扩增的T细胞受体克隆。尽管需要在更大的队列中进行进一步验证，但我们的数据表明，T细胞受体多样性测量可能成为研究糖尿病的有价值工具，例如将多样性作为区分不同类型糖尿病的指标。
