Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2024

Circulating CXCR3+ CCR4+ and regulatory high-risk HLA class II-restricted islet-specific T cell phenotypes predict poor clinical outcome in children with T1D. (#181)

Gayathri M 1 2 , Hanno Nel 1 2 , Emma Hamilton-Williams 1 2 , Hugh Reid 3 , Mai Thao T Tran 3 , Jamie Rossjohn 4 , Kerry Buchanan 5 , Ranjeny Thomas 1 2
  1. Frazer Institute, The University of Queensland, Brisbane
  2. Translational Research Institute, South Brisbane, QUEENSLAND, Australia
  3. Biochemistry and Molecular Biology, Monash University, Melbourne
  4. Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Melbourne
  5. Children's Health Queensland Clinical Unit, The University of Queensland, Brisbane

There is a growing need to identify biomarkers of Type 1 diabetes (T1D) progression to determine the efficacy and durability of therapies in clinical trials. Studies have found that a stronger proinflammatory immune landscape predicted faster beta cell decline during partial remission in subjects with T1D. Due to the well-documented, disease-causing role of islet-specific T cells, we aimed to characterise these cells in relation to clinical outcome in subjects with T1D. Using multiplexed HLADR4/DQ8-restricted proinsulin (PI) and PI- hybrid insulin peptide (HIP) tetramers in a comprehensive T cell phenotyping spectral flow cytometry panel, we stained frozen PBMC samples from patients, ex vivo. We found a disease-specific enrichment of CXCR3+ CCR4+ and exhausted regulatory T cell (Treg) phenotypes within islet-specific T cells. Interestingly, these phenotypes which were significantly correlated with shorter partial remission duration in children with T1D. This suggests that the upregulation of specific chemokine receptors on islet-specific T cells may induce their migration to inflamed islets to exacerbate chronic inflammation. This association of CXCR3+ CXCR4+ islet-specific T cells with decreased length of partial remission was also reflected in the global CD4+ and CD8+ T cell compartments, highlighting the potential of these circulating double-positive T cells as robust biomarkers of disease progression and response to therapy in clinical trials.