T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients

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 tech...

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Main Authors: Yin Tong, Zhoufang Li, Hua Zhang, Ligang Xia, Meng Zhang, Ying Xu, Zhanhui Wang, Michael W. Deem, Xiaojuan Sun, Jiankui He
Format: Article
Language:English
Published: Elsevier 2016-12-01
Series:Genomics, Proteomics & Bioinformatics
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S167202291630184X
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author Yin Tong
Zhoufang Li
Hua Zhang
Ligang Xia
Meng Zhang
Ying Xu
Zhanhui Wang
Michael W. Deem
Xiaojuan Sun
Jiankui He
author_facet Yin Tong
Zhoufang Li
Hua Zhang
Ligang Xia
Meng Zhang
Ying Xu
Zhanhui Wang
Michael W. Deem
Xiaojuan Sun
Jiankui He
author_sort Yin Tong
collection DOAJ
description 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.
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spelling doaj.art-f34d9d8b157f4b6896f651827805591f2024-02-02T11:59:37ZengElsevierGenomics, Proteomics & Bioinformatics1672-02292016-12-0114633834810.1016/j.gpb.2016.10.003T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes PatientsYin Tong0Zhoufang Li1Hua Zhang2Ligang Xia3Meng Zhang4Ying Xu5Zhanhui Wang6Michael W. Deem7Xiaojuan Sun8Jiankui He9Department of Biology, South University of Science and Technology of China, Shenzhen 518055, ChinaDepartment of Biology, South University of Science and Technology of China, Shenzhen 518055, ChinaDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, ChinaDepartment of Gastrointestinal Surgery, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518020, ChinaDepartment of Biology, South University of Science and Technology of China, Shenzhen 518055, ChinaDepartment of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartments of Bioengineering and Physics & Astronomy, Rice University, Houston, TX 77005, USAShenzhen Tumor Immune-Gene Therapy Clinical Application Engineering Lab, Biobank of the Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, ChinaDepartment of Biology, South University of Science and Technology of China, Shenzhen 518055, ChinaType 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.http://www.sciencedirect.com/science/article/pii/S167202291630184XDiversityHigh-throughput sequencingImmune repertoireT cell receptorType 1 diabetes
spellingShingle Yin Tong
Zhoufang Li
Hua Zhang
Ligang Xia
Meng Zhang
Ying Xu
Zhanhui Wang
Michael W. Deem
Xiaojuan Sun
Jiankui He
T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
Genomics, Proteomics & Bioinformatics
Diversity
High-throughput sequencing
Immune repertoire
T cell receptor
Type 1 diabetes
title T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
title_full T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
title_fullStr T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
title_full_unstemmed T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
title_short T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
title_sort t cell repertoire diversity is decreased in type 1 diabetes patients
topic Diversity
High-throughput sequencing
Immune repertoire
T cell receptor
Type 1 diabetes
url http://www.sciencedirect.com/science/article/pii/S167202291630184X
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