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

A Corrigendum to this article was published on 06 May 1999

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 CD4CD8 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.

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Figure 1: CD4CD8 Vα24JαQ T-cell clones respond to C1R/CD1d transfectants specifically.
Figure 2: Specificity of three CD4CD8 Vα24JαQ T-cell clones for CD1 isoforms.
Figure 3: IL-4 and IFN-γ secretion profiles of CD4CD8 Vα24JαQ T-cell clones raised from monozygotic twins and triplets discordant for IDDM.
Figure 4: Serum IL-4 and IFN-γ in type 1 diabetes.

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Acknowledgements

We thank the DFCI flow cytometry facility for cell sorting, T. Smith for patient support, J. Orov for statistical analysis and A. LaMothe for clerical support. We wish to specifically thank the patients for their generosity without which these studies could not have been performed. These studies were supported by grants from the NIAID of the NIH.

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Wilson, S., Kent, S., Patton, K. et al. Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes. Nature 391, 177–181 (1998). https://doi.org/10.1038/34419

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