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Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235667 | GEO | 2023/07/06

REPOSITORIES: GEO

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Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [Fluidigm]

Project description:The endocrine pancreas is one of the most inaccessible organs of the human body. Its autoimmune attack leads to type 1 diabetes (T1D) in a genetically susceptible population and a lifelong need for exogenous insulin replacement. Monitoring disease progression by sampling peripheral blood would provide key insights into T1D immune-mediated mechanisms and potentially change preclinical diagnosis and the evaluation of therapeutic interventions. This effort has been limited to the measurement of circulating anti-islet antibodies, which despite a recognized diagnostic value, remain poorly predictive at the individual level for a fundamentally CD4 T cell-dependent disease. Here, peptide-major histocompatibility complex tetramers were used to profile blood anti-insulin CD4 T cells in mice and human. While percentages of these were not directly informative, the state of activation of anti-insulin T cells measured by RNA and protein profiling was able to distinguish normalcy versus disease progression. Activated anti-insulin CD4 T cell were detected at time of diagnosis but also in patients with established disease and in some at-risk individuals. These results support the concept that antigen specific CD4 T cells might be used to monitor autoimmunity in real time. This advance can inform our approach to T1D diagnosis and therapeutic interventions in the pre-clinical phase of anti-islet autoimmunity.

2023-07-06 | GSE235123 | GEO

Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen specific CD4 T cells [TCR-Seq]

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