title: T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients.
abstract: 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.
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Zhoufang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhanhui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Departments of Bioengineering and Physics & Astronomy, Rice University, Houston, TX 77005, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Deem
authors.affiliation: Shenzhen Tumor Immune-Gene Therapy Clinical Application Engineering Lab, Biobank of the Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China. Electronic address: xiaojuan26@gmail.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen 518055, China. Electronic address: hejk@sustc.edu.cn.
authors.forename: Jiankui
authors.initials: J
authors.lastname: He
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D000072417:Protein Domains; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: Diversity; High-throughput sequencing; Immune repertoire; T cell receptor; Type 1 diabetes