CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes

• Published in: Journal of autoimmunity Vol. 50; pp. 77 - 82
• Main Authors: Sarikonda, Ghanashyam, Pettus, Jeremy, Phatak, Sonal, Sachithanantham, Sowbarnika, Miller, Jacqueline F, Wesley, Johnna D, Cadag, Eithon, Chae, Ji, Ganesan, Lakshmi, Mallios, Ronna, Edelman, Steve, Peters, Bjoern, von Herrath, Matthias
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.05.2014; Elsevier
• Subjects: Adult; Aged; Allergy and Immunology; Antigen specific T-cells; Autoantigens - immunology; Biological and medical sciences; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8+ T-cells; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cytotoxicity, Immunologic; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; ELISpot; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme-Linked Immunospot Assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HLA-Qdot-multimer analysis; Humans; Interferon-gamma - biosynthesis; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Longitudinal Studies; Male; Medical sciences; Middle Aged; Type 1 diabetes; Antigen specific T-cells; HLA-Qdot-multimer analysis; Type 1 diabetes; CD8 + T-cells; ELISpot; CD8+ T-cells; Endocrinopathy; Type 2 diabetes; T-cells; Immunopathology; HLA-System; CD4 T lymphocyte; Major histocompatibility system; Autoimmune disease; Metabolic diseases; Enzyme immunoassay; Immunology; Reactivity; CD8; T-Lymphocyte; Antigen specific; Class I histocompatibility antigen; CD8 T lymphocyte; CD8(+) T-cells
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2013.12.003

Abstract Previous cross-sectional analyses demonstrated that CD8+ and CD4+ T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4+ T-cell cytokine production and autoreactive CD8+ T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4+ T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8+ T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4+ T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8+ T-cells and more rapid beta-cell loss. In conclusion, CD4+ T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8+ T-cells are unique to T1D. Thus, autoreactive CD8+ cells may serve as a more T1D-specific biomarker.