Clinical trial NCT03236558: The Role of the Thymus in Type I Diabetes.
Official title: Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Type1 Diabetes
Keywords: Type 1 diabetes
Juvenile diabetes
Immune-tolerance
Regulatory T lymphocyte
Treg
TCR
Repertoire
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Centre National de la Recherche Scientifique, France
First posted: 2017-08-02
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls.
timeFrame: Day 1
Secondary outcomes:
measure: Ratio between TCR diversities expressed by Treg cells vs. conventional T cells.
timeFrame: Day 1
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU de Toulouse
state: Midi-Pyrénées
Study officials:
affiliation: CHU Toulouse
name: Claire Le Tallec, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferreira C, Singh Y, Furmanski AL, Wong FS, Garden OA, Dyson J. Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8320-5. doi: 10.1073/pnas.0808493106. Epub 2009 Apr 9.
citation: Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, van Meerwijk JP, Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 2015 Jun;16(6):628-34. doi: 10.1038/ni.3150. Epub 2015 May 4.
citation: Steffens CM, Al-Harthi L, Shott S, Yogev R, Landay A. Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): differential correlation between adult and pediatric TRECs and naive phenotypes. Clin Immunol. 2000 Nov;97(2):95-101. doi: 10.1006/clim.2000.4938.
citation: Calder AE, Hince MN, Dudakov JA, Chidgey AP, Boyd RL. Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation. 2011;18(5):281-9. doi: 10.1159/000329496. Epub 2011 Sep 22.
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