Fulminant type 1 diabetes patients display high frequencies of IGRP-specific type 1 CD8+ T cells

Abstract

The role of cellular autoimmunity in the pathogenesis of fulminant type 1 diabetes (FT1D) remains largely unknown. In this study, we performed an integrated assay using peripheral blood mononuclear cells to determine the islet antigen-specific CD8⁺ T cell responses in FT1D and compare the responses among acute-onset T1D (AT1D) and slowly progressive T1D (SP1D). IGRP- and ZnT8-specific IL-6, G-CSF, and TNF-α responses were significantly upregulated in patients with FT1D, while IGRP- and ZnT8-specific IP-10 responses were significantly upregulated in patients with AT1D than in non-diabetics (ND). Furthermore, the frequencies of IGRP-specific type 1 CD8⁺ cytotoxic T (Tc1) cells were significantly higher in the FT1D group than in the ND, SP1D, and AT1D groups. Additionally, IGRP-specific Tc1 cells were more abundant in the FT1D with HLA-A2 group than in the FT1D without A2 group. In conclusion, our study suggests that IGRP-specific CD8⁺ T cells significantly contribute to the pathogenesis of FT1D.

Keywords: CD8(+) T cells; Cytokine; Islet-specific glucose-6-phosphatase catalytic subunit-related protein; Type 1 diabetes.