CD8 and cytotoxic T cells in type 1 diabetes

The intra-islet cellular infiltrate found at post mortem in patients with new-onset Type 1 diabetes mellitus (T1DM) comprises both CD4+ and CD8+ cells, yet very few studies have investigated CD8 T cell responses to islet autoantigens. We therefore examined the response of peripheral blood CD8 T cells from new-onset T1DM patients and control subjects possessing HLA-A*0201 genes to potential CD8 T cell epitopes contained in a panel of peptides derived from proinsulin, glutamic acid decarboxylase, islet-specific glucose-6-phosphatase catalytic subunit-related protein and islet amyloid polypeptide, each putatively presented by the HLA class I molecule, HLA-A2.1 (A*0201) using a variety of techniques including in vitro culture with peptide, enzyme-linked immunospot (ELISPOT) assay and HLA tetramers. We find CD8 T cells present using these techniques, some of which have cytotoxic activity. The demonstration that rare islet autoreactive CD8 T cells are detectable in blood should promote mechanistic studies on these cells, as well as advancing T cell assay development.