Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes

• Published in: Nature (London) Vol. 391; no. 6663; pp. 177 - 181
• Main Authors: Schatz, Desmond A, Wilson, S. Brian, Kent, Sally C, Patton, Kurt T, Orban, Tihamer, Jackson, Richard A, Exley, Mark, Porcelli, Steven, Atkinson, Mark A, Balk, Steven P, Strominger, Jack L, Hafler, David A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 08.01.1998
• Subjects: Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Medical sciences; Endocrinopathy; Human; T cell receptor; Genetic variant; Etiopathogenesis; T-Lymphocyte; Insulin dependent diabetes; Autoimmune disease; Cell subpopulation; Twin
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/34419

Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) is a disease controlled by the major histocompatibility complex (MHC) which results from T-cell-mediated destruction of pancreatic β-cells. The incomplete concordance in identical twins and the presence of autoreactive T cells and autoantibodies in individuals who do not develop diabetes suggest that other abnormalities must occur in the immune system for disease to result,. We therefore investigated a series of at-risk non-progressors and type1 diabetic patients (including five identical twin/triplet sets discordant for disease). The diabetic siblings had lower frequencies of CD4−CD8− Vα24JαQ+ T cells compared with their non-diabetic sibling. All 56 Vα24JαQ+ clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-γ upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-γ. Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-γ. These results support a model for IDDM in which Th1-cell-mediated tissue damage is initially regulated by Vα24JαQ+ T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM.