Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes

Nature. 1998 Jan 8;391(6663):177-81. 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 beta-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- Valpha24JalphaQ+ T cells compared with their non-diabetic sibling. All 56 Valpha24JalphaQ+ clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-gamma upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-gamma. Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-gamma. These results support a model for IDDM in which Thl-cell-mediated tissue damage is initially regulated by Valpha24JalphaQ+ T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Twin Study

MeSH terms

  • Antigens, CD1 / immunology
  • Cells, Cultured
  • Clone Cells
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression
  • Diseases in Twins
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Lymphocyte Count
  • Male
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology*
  • Triplets
  • Twins, Monozygotic


  • Antigens, CD1
  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • Interferon-gamma