T-cell reactivity to beta-cell membrane antigens associated with beta-cell destruction in IDDM

Diabetes. 1995 Mar;44(3):278-83. doi: 10.2337/diab.44.3.278.

Abstract

Insulin-dependent diabetes mellitus (IDDM) results from a T-cell-mediated destruction of the insulin-producing beta-cells. In this study, we designed a sensitive assay to detect and identify islet cell-reactive T-cells in patients with newly diagnosed IDDM. The relation between T-cell recognition of beta-cell antigens with IDDM and the pathogenesis of the disease (the beta-cell destruction process) was tested in a large group of IDDM patients and compared with T-cell responses in nondiabetic children with other chronic inflammations and in immunologically normal, age-matched control subjects. The results demonstrate that peripheral blood T-cells reacting with a beta-cell membrane preparation enriched for insulin-secretory granule antigen were detectable in the majority of newly diagnosed IDDM patients (27 of 40 [67%]; mean stimulation index [SI] 37.0). Such reactivity was reduced postonset in IDDM patients proportionally to the duration of the disease (11 of 30 [37%]; mean SI 8.7). Nondiabetic age-matched control subjects showed no responses or moderate responses to the granule preparation (4 of 48 [8%]; mean SI 3.4). The magnitude of the T-cell response was significantly greater in newly diagnosed IDDM patients than in IDDM patients tested at least 2 years postonset (P < 0.001). Two children in remission for insulin dependency (so-called honeymoon period) displayed exceptionally high proliferative responses to insulin-secretory granules (mean SI 86.7). These results imply that T-cell recognition of insulin-secretory granule antigens is associated with IDDM and in particular with the immune-mediated process of beta-cell destruction.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, Surface / immunology*
  • Cell Membrane / immunology
  • Child
  • Child, Preschool
  • Cryopreservation
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Humans
  • Infant
  • Inflammation / immunology
  • Insulinoma / immunology
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology*
  • Lymphocyte Activation
  • Male
  • Pancreatic Neoplasms / immunology
  • Rats
  • Reference Values
  • T-Lymphocytes / immunology*
  • Tetanus Toxoid / immunology

Substances

  • Antigens, Surface
  • Tetanus Toxoid