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

During the development of type 1 diabetes (T1DM), regulatory T cells (Treg) are modified and their protective role is no longer optimal, particularly against pathology-specific autoreactive antigens. The hypothesis is that in patients with T1DM, the function and phenotype of Treg cells, as well as their receptor repertoire for the antigen to which they are specific (TCR), no longer allow them to control tolerance. The in-depth study of these cells, at both genetic and molecular levels, will enable a major breakthrough in our understanding of the pathophysiology of T1DM, and in the development of targeted cell therapy.

The investigators expect major/important differences between patient Tregs and those of the control population in this study, at the molecular, phenotypic and functional levels. These differences will highlight the TCRs recognizing the target self-antigens. In this way, investigators expect to be able to select a limited number of Treg TCRs that could ultimately be used in cell therapy to restore the protective role of Tregs in these patients.

Thus, this knowledge will enable to propose in the future a more effective immunotherapy with a long-term effect, in order to improve the management of patients with autoimmune diabetes and potentially cure them.

Accordingly, yhe investigators will study insulin-specific Tregs in T1DM patients and control individuals, as well as conventional T cells directed against the same antigen, which in patients are implicated in the disease. This will include a study of their functional status, their transcriptomic profile, as well as their TCRs and their fine recognition properties of the major diabetes self-antigen, insulin.

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