Tracking GAD-specific T cell expansions in type 1 diabetes by intradermal GAD-alum challenge
Department
Research
Document Type
Article
Publication Title
JCI Insight
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.
First Page
e203119
DOI
10.1172/jci.insight.203119
Volume
11
Issue
20
Publication Date
10-22-2026
Medical Subject Headings
Diabetes Mellitus, Type 1; Glutamate Decarboxylase; Animals; Mice; Female; Lymph Nodes; Receptors, Antigen, T-Cell; Skin; Humans; Injections, Intradermal; CD4-Positive T-Lymphocytes; Autoantigens; T-Lymphocytes
PubMed ID
42678730
Recommended Citation
Hanna, S. J., Robinson, E. J., Thayer, T. C., Nakayama, M., Landry, L., Andrews, R., Dolton, G., Davies, J., Williams, E., Pearson, J. A., Sewell, A. K., Narendran, P., Wraith, D. C., Howell, A., Young, P., Hart, M., Lindqvist, A., Wong, F. S., Tree, T. I., Dayan, C. M., & Tatovic, D. (2026). Tracking GAD-specific T cell expansions in type 1 diabetes by intradermal GAD-alum challenge. JCI Insight, 11 (20), e203119. https://doi.org/10.1172/jci.insight.203119