Type1 Diabetes
Conditions
Keywords
Type 1 diabetes, Juvenile diabetes, Immune-tolerance, Regulatory T lymphocyte, Treg, TCR, Repertoire
Brief summary
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
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.
Interventions
PROCEDUREBlood collection
Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Centre National de la Recherche Scientifique, France
University Hospital, Toulouse
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls. | Day 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio between TCR diversities expressed by Treg cells vs. conventional T cells. | Day 1 | 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. |
Countries
France
Outcome results
None listed