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 and David A. Hafler
Additional contact information
S. Brian Wilson: Harvard University
Sally C. Kent: Center for Neurologic Diseases, Brigham and Women's Hospital, Brigham and Women's Hospital Harvard Medical School
Kurt T. Patton: Center for Neurologic Diseases, Brigham and Women's Hospital, Brigham and Women's Hospital Harvard Medical School
Tihamer Orban: Immunology Section, Joslin Diabetes Center, Brigham and Women's Hospital Harvard Medical School
Richard A. Jackson: Immunology Section, Joslin Diabetes Center, Brigham and Women's Hospital Harvard Medical School
Mark Exley: Cancer Biology Program, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital Harvard Medical School
Steven Porcelli: Lymphocyte Biology Section, Immunology and Allergy, Brigham and Women's Hospital Harvard Medical School
Desmond A. Schatz: University of Florida
Mark A. Atkinson: University of Florida
Steven P. Balk: Cancer Biology Program, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital Harvard Medical School
Jack L. Strominger: Harvard University
David A. Hafler: Center for Neurologic Diseases, Brigham and Women's Hospital, Brigham and Women's Hospital Harvard Medical School

Nature, 1998, vol. 391, issue 6663, 177-181

Abstract: 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.

Date: 1998
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DOI: 10.1038/34419

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