Narrowing in on the anti-beta cell-specific T cells: looking 'where the action is'
Department of Medicine, Division of Diabetes; Diabetes Center of Excellence
Endocrine System Diseases | Endocrinology, Diabetes, and Metabolism | Immunopathology
PURPOSE OF REVIEW: By necessity, the vast majority of information we have on autoreactive T cells in human type 1 diabetes (T1D) has come from the study of peripheral blood of donors with T1D. It is not clear how representative the peripheral autoreactive T-cell repertoire is of the autoreactive T cells infiltrating the islets in T1D. We will summarize and discuss what is known of the immunohistopathology of insulitis, the T-cell receptor repertoire expressed by islet-infiltrating T cells, and the autoreactivity and function of islet-infiltrating T cells in T1D.
RECENT FINDINGS: Recovery and analysis of live, islet-infiltrating T cells from the islets of cadaveric donors with T1D revealed a broad repertoire and proinflammatory phenotype of CD4 T-cell autoreactivity to peptide targets from islet proteins, including proinsulin, as well as CD4 T-cell reactivity to a number of post-translationally modified peptides, including peptides with citrullinations and hybrid insulin peptide fusions. Islet-infiltrating CD8 T cells were also derived and required further isolation and characterization.
SUMMARY: The recovery of live, islet-infiltrating T cells from donors with T1D, reactive with a broad range of known targets and post-translationally modified peptides, allows for the specific functional analysis of islet-infiltrating T cells for the development of antigen-specific immunotherapies.
DOI of Published Version
Curr Opin Endocrinol Diabetes Obes. 2017 Apr;24(2):98-102. doi: 10.1097/MED.0000000000000323. Link to article on publisher's site
Current opinion in endocrinology, diabetes, and obesity
Kent SC, Babon JA. (2017). Narrowing in on the anti-beta cell-specific T cells: looking 'where the action is'. Open Access Publications by UMMS Authors. https://doi.org/10.1097/MED.0000000000000323. Retrieved from https://escholarship.umassmed.edu/oapubs/3141