Tracking GAD-specific T cell expansions in type 1 diabetes by intradermal GAD-alum challenge
8 affiliations
- 1Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
- 2Division of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
- 3Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, New York, USA.
- 4Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, USA.
- 5Department of Immunobiology, School of Immunology & Microbial Sciences, King’s College London, London, United Kingdom.
- 6Breast Test Wales, Public Health Wales, Cardiff, United Kingdom.
- 7Department of Radiology, University Hospital of Wales, Cardiff, United Kingdom.
- 8Diamyd Medical AB, Stockholm, Sweden.
Abstract
Identifying and monitoring autoreactive T cells that drive β cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of glutamic acid decarboxylase (GAD)-alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNA-seq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally expanded and 4 of 14 (28%) re-expressed TCRs were GAD reactive. In LNs, 1 of 14 (4%) clonally expanded TCRs was GAD reactive, representing approximately 0.08% of all T cells. GAD-reactive cells across compartments displayed Th1- and Th17-associated transcription signatures. These results demonstrate that intradermal autoantigen challenge and scRNA-seq enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.
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BibTeX
@article{hanna2026tracking,
title = {{Tracking GAD-specific T cell expansions in type 1 diabetes by intradermal GAD-alum challenge}},
author = {Stephanie J. Hanna and Emma J.S. Robinson and Terri C. Thayer and Maki Nakayama and Laurie Landry and Robert Andrews and Garry Dolton and Joanne Davies and Evangelia Williams and James A. Pearson and Andrew K. Sewell and Parth Narendran and David C. Wraith and Alexandra Howell and Philippa Young and Mary Hart and Anton Lindqvist and F. Susan Wong and Tim I.M. Tree and Colin M. Dayan and Danijela Tatovic},
journal = {JCI Insight},
year = {2026},
month = sep,
doi = {10.1172/jci.insight.203119},
url = {https://doi.org/10.1172/jci.insight.203119},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tracking GAD-specific T cell expansions in type 1 diabetes by intradermal GAD-alum challenge
AU - Stephanie J. Hanna
AU - Emma J.S. Robinson
AU - Terri C. Thayer
AU - Maki Nakayama
AU - Laurie Landry
AU - Robert Andrews
AU - Garry Dolton
AU - Joanne Davies
AU - Evangelia Williams
AU - James A. Pearson
AU - Andrew K. Sewell
AU - Parth Narendran
AU - David C. Wraith
AU - Alexandra Howell
AU - Philippa Young
AU - Mary Hart
AU - Anton Lindqvist
AU - F. Susan Wong
AU - Tim I.M. Tree
AU - Colin M. Dayan
AU - Danijela Tatovic
PY - 2026
DA - 2026/09/01
JO - JCI Insight
DO - 10.1172/jci.insight.203119
UR - https://doi.org/10.1172/jci.insight.203119
AB - Identifying and monitoring autoreactive T cells that drive β cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of glutamic acid decarboxylase (GAD)-alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNA-seq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally expanded and 4 of 14 (28%) re-expressed TCRs were GAD reactive. In LNs, 1 of 14 (4%) clonally expanded TCRs was GAD reactive, representing approximately 0.08% of all T cells. GAD-reactive cells across compartments displayed Th1- and Th17-associated transcription signatures. These results demonstrate that intradermal autoantigen challenge and scRNA-seq enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.
SN - 2379-3708
ER -