Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals

Summary

Type 1 diabetes (T1D) is caused by an autoimmune response leading to the destruction of pancreatic beta cells. The disease association with particular HLA class II alleles, particularly HLA-DQ8, indicates the implication of CD4 T cells in its aetiology. The hypothesis is therefore that T1D starts by the loss of tolerance in autoreactive CD4 T cells. This might result from alterations in conventional autoreactive CD4 T cells (Tcons), which drive disease, or autoreactive regulatory CD4 T cells expressing the transcription factor FOXP3 (Tregs), which normally maintain immune tolerance. The investigators expect that the characterization of HLA-DQ8-restricted Tcons and Tregs in recent onset HLA-DQ8+ T1D patients shall shed light on the molecular mechanisms underpinning T1D development. This knowledge will guide the development of novel cell therapies harnessing the power of genetically engineered Tregs expressing the relevant antigen receptor to restore immune homeostasis upon cell transfer. The ultimate goal is to reach a curative effect

Eligibility

Inclusion Criteria:

Newly diagnosed T1DM group:

* Age ≥ 2 years and \< 18 years on day of inclusion;
* Weight ≥ 12 kg;
* Newly diagnosed T1DM, diagnosis defined according to International Society of Pediatric and Adolescent Diabetes (ISPAD) criteria by: hyperglycemia \> 2g/L and/or ketonemia and/or polyuro-polydipsia and/or weight loss ;
* Absence of other associated inflammatory or autoimmune diseases;
* Affiliation with a health insurance scheme or beneficiary (excluding AME);
* Written consent of parental guardians;
* Ability to understand and read French.

Control group :

* Age ≥ 2 years and \< 18 years on the day of inclusion;
* Weight ≥ 12 kg;
* No personal history of T1DM;
* Affiliation with a health insurance scheme or entitled person (excluding AME);
* Written consent from parental guardians;
* Ability to understand and read French.

Exclusion Criteria:

Newly diagnosed T1DM group:

* Use of oral or intravenous corticosteriods in the month prior to blood sampling
* Contraindication to the use of anaesthetic cream for blood sampling.

Control group :

* History of autoimmune or inflammatory disease
* Use of oral or intravenous corticosteriods in the month prior to blood sampling
* Contraindication to the use of anaesthetic cream for blood sampling

Conditions2

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