High-Throughput Sequencing of Islet-Infiltrating Memory CD4+ T Cells Reveals a Similar Pattern of TCR Vβ Usage in Prediabetic and Diabetic NOD Mice

Marrero, Idania; Hamm, David; Davies, Joanna D.

doi:10.1371/journal.pone.0076546

Cited by 26 publications

(33 citation statements)

References 55 publications

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“…Our results are consistent with previous studies using T1D mouse models, in which HECs are frequently observed in islet-infiltrating T cells [31], [32], [33]. The significant difference in the number and percentage of HECs between T1D and T2D samples indicates that the quantification of HECs and diversity could be a potential indicator of T1D.…”

Section: Resultssupporting

confidence: 92%

T Cell Repertoire Diversity is Decreased in Type 1 Diabetes Patients

Tong¹,

Li²,

Zhang³

et al. 2016

Genomics, Proteomics &Amp; Bioinformatics

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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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Section: Resultssupporting

confidence: 92%

T Cell Repertoire Diversity is Decreased in Type 1 Diabetes Patients

Tong¹,

Li²,

Zhang³

et al. 2016

Genomics, Proteomics &Amp; Bioinformatics

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show abstract

“…This is similar to shared clonotypes of islet infiltrating T cells in mice with type one diabetes. 21 The relatively low frequency of unique TCR clonotypes in hypertensive mice is consistent with a common pattern of inflammation where specific T cell clones are first activated, followed by infiltration of other T cells unrelated to the initial clone that then contribute to the inflammatory response. 22 In addition, in a region of inflammation, there may be development of other antigens, due to protein modifications that lead to activation of T cells other than the originally stimulated clones.…”

Section: Discussionsupporting

confidence: 54%

Oligoclonal CD8 ⁺ T Cells Play a Critical Role in the Development of Hypertension

et al. 2014

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Recent studies have emphasized a role of adaptive immunity, and particularly T cells, in the genesis of hypertension. We sought to determine the T cell subtypes that contribute to hypertension and renal inflammation in angiotensin II-induced hypertension. Using T cell receptor (TCR) spectratyping to examine TCR usage we demonstrated that CD8+ cells, but not CD4+ cells, in the kidney exhibited altered TCR transcript lengths in Vβ3, 8.1 and 17 families in response to angiotensin II-induced hypertension. Clonality was not observed in other organs. The hypertension caused by angiotensin II in CD4−/− and MHCII−/− mice was similar to that observed in WT mice, while CD8−/− mice and OT1xRAG-1−/− mice, which have only one TCR, exhibited a blunted hypertensive response to angiotensin II. Adoptive transfer of pan-T cells and CD8+ T cells but not CD4+/CD25− cells conferred hypertension to RAG-1−/− mice. In contrast, transfer of CD4+/CD25+ cells to wild type mice receiving angiotensin II decreased blood pressure. Mice treated with angiotensin II exhibited increased numbers of kidney CD4+ and CD8+ T cells. In response to a sodium/volume challenge, wild type and CD4−/− mice infused with angiotensin II retained water and sodium whereas CD8−/− mice did not. CD8−/− mice were also protected against angiotensin-induced endothelial dysfunction and vascular remodeling in the kidney. These data suggest that in the development of hypertension, an oligoclonal population of CD8+ cells accumulate in the kidney and likely contribute to hypertension by contributing to sodium and volume retention and vascular rarefaction.

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“…Deep Sequencing-CD4 ϩ T cells (10 6 ) were isolated from the spleens of treated (ovalbumin and PSA) or untreated (saline) mice and sent to Adaptive Biotechnologies for RNA extraction and deep sequencing of the TCR ␤-chain using their proprietary assay platform, as reported elsewhere (22). Data analysis was performed using Adaptive Biotechologies immunoSEQ web tools and graphed using GraphPad Prism (version 5.0).…”

Section: Methodsmentioning

confidence: 99%

Polysaccharide A from the Capsule of Bacteroides fragilis Induces Clonal CD4+ T Cell Expansion

Johnson

Jones

Cobb

2015

Journal of Biological Chemistry

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High-Throughput Sequencing of Islet-Infiltrating Memory CD4+ T Cells Reveals a Similar Pattern of TCR Vβ Usage in Prediabetic and Diabetic NOD Mice

Cited by 26 publications

References 55 publications

T Cell Repertoire Diversity is Decreased in Type 1 Diabetes Patients

T Cell Repertoire Diversity is Decreased in Type 1 Diabetes Patients

Oligoclonal CD8 ⁺ T Cells Play a Critical Role in the Development of Hypertension

Polysaccharide A from the Capsule of Bacteroides fragilis Induces Clonal CD4+ T Cell Expansion

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High-Throughput Sequencing of Islet-Infiltrating Memory CD4+ T Cells Reveals a Similar Pattern of TCR Vβ Usage in Prediabetic and Diabetic NOD Mice

Cited by 26 publications

References 55 publications

T Cell Repertoire Diversity is Decreased in Type 1 Diabetes Patients

T Cell Repertoire Diversity is Decreased in Type 1 Diabetes Patients

Oligoclonal CD8 + T Cells Play a Critical Role in the Development of Hypertension

Polysaccharide A from the Capsule of Bacteroides fragilis Induces Clonal CD4+ T Cell Expansion

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Resources

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Oligoclonal CD8 ⁺ T Cells Play a Critical Role in the Development of Hypertension