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

S. Brian Wilson, Sally C. Kent, Kurt T. Patton, Tihamer Orban, Richard A. Jackson, Mark Exley, Steven Porcelli, Desmond A. Schatz, Mark A. Atkinson, Steven P. Balk, Jack L. Strominger, David A. Hafler

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617 Scopus citations

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-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 type 1 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.

Original languageEnglish (US)
Pages (from-to)177-181
Number of pages5
JournalNature
Volume391
Issue number6663
DOIs
StatePublished - Jan 8 1998
Externally publishedYes

ASJC Scopus subject areas

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    Wilson, S. B., Kent, S. C., Patton, K. T., Orban, T., Jackson, R. A., Exley, M., Porcelli, S., Schatz, D. A., Atkinson, M. A., Balk, S. P., Strominger, J. L., & Hafler, D. A. (1998). Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes. Nature, 391(6663), 177-181. https://doi.org/10.1038/34419