Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients

Diabetologia. 1995 Aug;38(8):953-8. doi: 10.1007/BF00400585.

Abstract

The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed (< 3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals and patients were compared, we found that bcl-2 expression within the CD3+ and CD4+ CD45R0+ T-cell populations was reduced significantly in IDDM patients (46.8 +/- 15.4 vs 79.6 +/- 11.7; 25.7 +/- 3.8 vs 47.15 +/- 5.7, respectively; p < 0.001). To establish whether low bcl-2 expression in T cells from newly-diagnosed patients reflects their susceptibility to death by an apoptotic process, we also evaluated DNA staining with propidium iodide in CD3+ lymphocyte suspension after a (24-72 h) culture period (spontaneous apoptosis). We found that IDDM patients have higher levels of spontaneous apoptosis (mean +/- SEM: 24 h = 4.6 +/- 0.8; 48 h = 9.9 +/- 1; 72 h = 12.8 +/- 1.1) than control subjects (24 h = 1.8 +/- 0.4; 48 h = 4.6 +/- 0.4; 72 h = 5.7 +/- 0.3; p < 0.02-0.001). Our study suggests that recent onset IDDM is characterised by reduced bcl-2 expression, which in turn may be associated with the increased spontaneous apoptosis we observed.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / blood
  • Apoptosis*
  • Autoantibodies / blood
  • Blood Glucose / analysis
  • CD3 Complex / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Family
  • Female
  • Flow Cytometry
  • Gene Expression*
  • Glycated Hemoglobin A / analysis
  • Humans
  • Male
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2
  • Reference Values
  • Risk Factors
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*

Substances

  • Antigens, CD
  • Autoantibodies
  • Blood Glucose
  • CD3 Complex
  • Glycated Hemoglobin A
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • islet cell antibody