The Role of the Thymus in Type I Diabetes.

Study Overview
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Brief Summary
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Regulatory T lymphocytes play a major role in the protection from autoimmune pathology. Defects in immunosuppression mediated by these cells is therefore suspected to contribute to these diseases. This issue has very little been studied in humans.Regulatory T cells emigrated from the thymus will be isolated from the blood of patients and healthy controls. The repertoire of antigen-receptors will be analysed by high throughput sequencing and its diversity estimated using appropriate statistical models borrowed from ecology.

Detailed Description
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In the thymus of an animal model of type I diabetes, the population of regulatory T cells expresses a repertoire of antigen receptors that is approximately ten-fold less diverse than that found in mice resistant to autoimmune pathology. Genetic models later showed that this reduced diversity was involved in the susceptibility to diabetes. Researchers study the diversity of the TCR expressed by regulatory T cells from paediatric type I diabetes patients and controls. Regulatory T cells emigrated from the thymus will be isolated from the blood of patients and healthy controls. The repertoire of antigen-receptors will be analysed by high throughput sequencing and its diversity estimated using appropriate statistical models borrowed from ecology.

Official Title
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Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.

Conditions
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Type1 Diabetes

Intervention / Treatment
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* Procedure: Blood collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type I diabetes patient having at least one age-matched sibling (healthy control) Exclusion Criteria: other immunopathology treatment with any anti-inflammatory or immunosuppressive drugs puberty legal protection

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with diabetes<br>T1D patients with blood collection | Procedure: Blood collection<br>* Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls. | Treg from the pediatric patients and the control subjects' blood will be isolated by cytometry, the messenger ribonucleic acid (mRNA) of these cells will be isolated, and the analysis of the alpha and beta chains of the TCRs will be carried out by high-throughput sequencing. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio between TCR diversities expressed by Treg cells vs. conventional T cells. | Treg from the pediatric patients and the control subjects' blood will be isolated by cytometry, the mRNA of these cells will be isolated, and the analysis of the alpha and beta chains of the TCRs will be carried out by high-throughput sequencing. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TCR, Type 1 diabetes, Juvenile diabetes, Immune-tolerance, Regulatory T lymphocyte, Treg, Repertoire