Deciphering the pathogenesis of human type 1 diabetes (T1D) by interrogating T cells from the “scene of the crime”
SC Kent, SI Mannering, AW Michels… - Current diabetes reports, 2017 - Springer
Current diabetes reports, 2017•Springer
Abstract Purpose of Review Autoimmune-mediated destruction of insulin-producing β-cells
within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable.
Previously, our understanding of the β-cell specific T cell repertoire was based on studies of
autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D;
more recently, investigations have included immunohistochemical analysis of some T cell
specificities in the pancreas from organ donors with T1D. Now, we are able to examine live …
within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable.
Previously, our understanding of the β-cell specific T cell repertoire was based on studies of
autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D;
more recently, investigations have included immunohistochemical analysis of some T cell
specificities in the pancreas from organ donors with T1D. Now, we are able to examine live …
Purpose of Review
Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D. Now, we are able to examine live, islet-infiltrating T cells from donors with T1D.
Recent Findings
Analysis of the T cell repertoire isolated directly from the pancreatic islets of donors with T1D revealed pro-inflammatory T cells with targets of known autoantigens, including proinsulin and glutamic acid decarboxylase, as well as modified autoantigens.
Summary
We have assayed the islet-infiltrating T cell repertoire for autoreactivity and function directly from the inflamed islets of T1D organ donors. Design of durable treatments for prevention of or therapy for T1D requires understanding this repertoire.
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