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...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 =Y3E-03 for CD8＋ T cells）. Furthermore, we iden- tified a group of highly-expanded T cell receptor clones that are shared by more than two TID 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.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.31200688,81470136,31401145,and 81372507)support from the International S&T Cooperation Program of China(Grant No.2014DFA31050)
文摘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 =Y3E-03 for CD8＋ T cells）. Furthermore, we iden- tified a group of highly-expanded T cell receptor clones that are shared by more than two TID 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.
