Autoreactive regulatory and conventional CD4 T cells in recent-onset type 1 diabetes

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

This project tests whether insulin-specific regulatory (Treg) and conventional (Tcon) CD4 T cells differ between children and adolescents newly diagnosed with type 1 diabetes and healthy control individuals.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 6 Years to 18 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Paris)
• Trial ID: NCT06427421 on ClinicalTrials.gov

What this trial studies

Researchers will recruit children and adolescents with recent-onset type 1 diabetes and age-matched healthy controls at Hôpital Necker Enfants Malades in Paris. They will perform HLA typing, beta-cell autoantibody measurements, flow cytometry to quantify Treg and Tcon frequency and phenotype, and isolate antigen-specific cells for TCR sequencing and RNA‑seq. Molecular, phenotypic and functional comparisons will be made to identify differences in autoreactive T cell repertoires and transcriptional programs. The ultimate aim is to pinpoint Treg TCRs that could be used to design antigen-specific engineered Treg cell therapies.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents (ages 2–17) newly diagnosed with type 1 diabetes, able to consent via a parent or guardian, without other inflammatory or autoimmune diseases, and willing to provide blood samples.

Not a fit: Patients with long-standing type 1 diabetes, adults, those recently treated with systemic corticosteroids, with other autoimmune/inflammatory diseases, or who cannot attend the Paris site or provide consent are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this work could identify antigen-specific Treg receptors to guide development of engineered Treg cell therapies that restore immune tolerance and slow or prevent beta-cell loss.

How similar studies have performed: Previous research has mapped autoreactive CD4 T cells and shown preclinical promise for antigen-specific Treg therapies, but clinical benefit in type 1 diabetes remains unproven.

Eligibility criteria

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

Where this trial is running

Paris

• Hôpital Necker Enfants Malades — Paris, France (Recruiting)

Study contacts

• Study coordinator: Jacques BELTRAND, MD, PhD

Conditions Type 1 Diabetes; Regulatory T cells; Pathophysiology of T1DM