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

Publisher Website
Google Scholar
Abstract
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-cells1. 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 result2,3. 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.

This publication has 27 references indexed in Scilit: