HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet ?-Cells From Donors With Type 1 Diabetes.

ABSTRACT: Type 1 diabetes studies consistently generate data showing islet ?-cell dysfunction and T cell-mediated anti-?-cell-specific autoimmunity. To explore the pathogenesis, we interrogated the ?-cell transcriptomes from donors with and without type 1 diabetes using both bulk-sorted and single ?-cells. Consistent with immunohistological studies, ?-cells from donors with type 1 diabetes displayed increased Class I transcripts and associated mRNA species. These ?-cells also expressed mRNA for Class II and Class II antigen presentation pathway components, but lacked the macrophage marker CD68. Immunohistological study of three independent cohorts of donors with recent-onset type 1 diabetes showed Class II protein and its transcriptional regulator Class II MHC trans-activator protein expressed by a subset of insulin+CD68- ?-cells, specifically found in islets with lymphocytic infiltrates. ?-Cell surface expression of HLA Class II was detected on a portion of CD45-insulin+ ?-cells from donors with type 1 diabetes by immunofluorescence and flow cytometry. Our data demonstrate that pancreatic ?-cells from donors with type 1 diabetes express Class II molecules on selected cells with other key genes in those pathways and inflammation-associated genes. ?-Cell expression of Class II molecules suggests that ?-cells may interact directly with islet-infiltrating CD4+ T cells and may play an immunopathogenic role.

SUBMITTER: Russell MA 

PROVIDER: S-EPMC6477908 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature