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
- PMID: 9498651
- DOI: 10.1007/s001250050887
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
Abstract
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.
Similar articles
-
1Alpha,25-dihydroxyvitamin D3 restores thymocyte apoptosis sensitivity in non-obese diabetic (NOD) mice through dendritic cells.J Autoimmun. 2005 Jun;24(4):281-9. doi: 10.1016/j.jaut.2005.03.007. J Autoimmun. 2005. PMID: 15913954
-
Early quantitative and functional deficiency of NK1+-like thymocytes in the NOD mouse.Eur J Immunol. 1996 Dec;26(12):2989-98. doi: 10.1002/eji.1830261226. Eur J Immunol. 1996. PMID: 8977295
-
Development of autoreactive diabetogenic T cells in the thymus of NOD mice.J Autoimmun. 2005 Feb;24(1):11-23. doi: 10.1016/j.jaut.2004.10.002. Epub 2004 Dec 8. J Autoimmun. 2005. PMID: 15725572
-
Defects in deletional tolerance of CD8+ T cells in autoimmune diabetes.Curr Dir Autoimmun. 2001;4:123-43. doi: 10.1159/000060533. Curr Dir Autoimmun. 2001. PMID: 11569400 Review. No abstract available.
-
Autoimmune disease. Gadding around the beta cell.Curr Biol. 1994 Feb 1;4(2):158-60. doi: 10.1016/s0960-9822(94)00038-2. Curr Biol. 1994. PMID: 7953521 Review.
Cited by
-
Animal models of spontaneous autoimmune diabetes: notes on their relevance to the human disease.Curr Diab Rep. 2004 Apr;4(2):151-4. doi: 10.1007/s11892-004-0071-z. Curr Diab Rep. 2004. PMID: 15035976 Review.
-
Genetic separation of the transplantation tolerance and autoimmune phenotypes in NOD mice.Rev Endocr Metab Disord. 2003 Sep;4(3):255-61. doi: 10.1023/a:1025152312496. Rev Endocr Metab Disord. 2003. PMID: 14501176 Review. No abstract available.
-
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes.Front Endocrinol (Lausanne). 2017 Dec 5;8:343. doi: 10.3389/fendo.2017.00343. eCollection 2017. Front Endocrinol (Lausanne). 2017. PMID: 29259578 Free PMC article. Review.
-
Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.Immunology. 2017 Feb;150(2):162-171. doi: 10.1111/imm.12674. Epub 2016 Oct 20. Immunology. 2017. PMID: 27649685 Free PMC article.
-
Up-regulation of fas and fasL pro-apoptotic genes expression in type 1 diabetes patients after autologous haematopoietic stem cell transplantation.Clin Exp Immunol. 2012 Jun;168(3):291-302. doi: 10.1111/j.1365-2249.2012.04583.x. Clin Exp Immunol. 2012. PMID: 22519592 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
