Resistance of T-cells to apoptosis in autoimmune diabetic (NOD) mice is increased early in life and is associated with dysregulated expression of Bcl-x

Diabetologia. 1998 Feb;41(2):178-84. doi: 10.1007/s001250050887.


Activated lymphocytes of autoimmune non-obese diabetic (NOD) mice exhibit an increased resistance to programmed cell death (PCD) following withdrawal of interleukin-2 (IL-2). In the present study, we found that resistance of NOD T lymphocytes to PCD was increased as early as 1 week of age, hence several weeks before the invasion of the pancreas by inflammatory cells, which is compatible with a role of the NOD apoptotic phenotype in the autoimmune susceptibility of this strain. In the thymus, mature single positive but not double positive or double negative thymocytes were more resistant to PCD in NOD compared to B6 mice. Moreover, in both NOD and B6 mice, CD4+ T cells were more resistant to PCD induced by IL-2 deprivation than CD8+ cells. As a result, NOD CD4+ T cells were remarkably resistant to cell death induced in this manner. In relation with this increased resistance to apoptosis, expression of the anti-apoptotic Bcl-x protein was upregulated in activated T cells of NOD mice, most notably after 24 h of IL-2 deprivation. These results should help us to understand the relationship of the NOD apoptotic phenotype to the emergence of the NOD mouse autoimmune disease.

Publication types

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

MeSH terms

  • Aging / immunology
  • Animals
  • Animals, Newborn
  • Apoptosis / immunology*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred NOD
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Thymus Gland / pathology
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein