Title

Narrowing in on the anti-beta cell-specific T cells: looking 'where the action is'

UMMS Affiliation

Department of Medicine, Division of Diabetes; Diabetes Center of Excellence

Date

4-1-2017

Document Type

Article

Disciplines

Endocrine System Diseases | Endocrinology, Diabetes, and Metabolism | Immunopathology

Abstract

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

10.1097/MED.0000000000000323

Comments

Curr Opin Endocrinol Diabetes Obes. 2017 Apr;24(2):98-102. doi: 10.1097/MED.0000000000000323. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Current opinion in endocrinology, diabetes, and obesity

PubMed ID

28099204