93-OR: Clonal Expansion of Islet Reactive CD4 T-Cells with Early Disease Progression in Type 1 Diabetes

• DOI: 10.2337/db24-93-or
• Publication Date: 2024-06-14T04:51:37Z
• Authors: THOMAS H. EDWARDS; JANICE CHEN; MATTHEW DUFORT; RACHEL HARTLEY; CATE SPEAKE; CARLA GREENBAUM; PETER LINSLEY; KAREN CEROSALETTI
• Keywords: CD154

Introduction & Objective: Islet antigen reactive (IAR) T cells play an important role in pancreatic β-cell destruction type 1 diabetes (T1D) and are clonally expanded after T1D diagnosis, indicative of vivo exposure. The objective this study was to determine if clonal expansion IAR CD4 occurs prior onset is associated with risk for disease progression. Methods: included prospective blood samples collected from islet autoantibody (Aab) positive individuals enrolled the TrialNet Pathways Prevention Long Term Investigative Follow-up studies. were isolated using a CD154 activation assay PBMC cross-sectional cohort Aab negative (n=6), Aab+ >18y <14y (n=3), >1 (n=6) donors increasing progression T1D. Cells analyzed by single-cell RNA-sequencing identify cell receptor α/β pairs full transcript profiles. Clonal visualized circos plots Simpson’s diversity. Transcript profiles unsupervised clustering differential gene expression Seurat v4. Results: observed primarily at-risk group compared single or groups. formed clusters based on differentiation status naïve effector memory phenotypes revealed enrichment subjects. Conclusion: These results suggest that profile may accompany multiple increased development Further studies longitudinal subjects progressing will validate extend these findings biomarker Disclosure T.H. Edwards: Employee; Wavely Diagnostics, Inc. J. Chen: None. M. Dufort: R. Hartley: C. Speake: Greenbaum: Other Relationship; Sanofi, Takeda Pharmaceutical Company Limited, Bristol-Myers Squibb Company, Imcyse. P. Linsley: K. Cerosaletti: Research Support; GentiBio, Cour Pharmaceuticals. Funding American Diabetes Association (1-19-ICTS-006)