Journal article
Deficient activation and resistance to activation-induced apoptosis of cd8 + t cells is associated with defective peripheral tolerance in nonobese diabetic mice
Clinical immunology (Orlando, Fla.), Vol.107(2), pp.103-115
2003
DOI: 10.1016/S1521-6616(03)00049-4
PMID: 12763479
Abstract
Activation-induced cell death (AICD) is a mechanism of homeostasis that limits the clonal expansion of autoreactive T cells and regulates central and peripheral tolerance. In nonobese diabetic (NOD) mice, defects in central and peripheral tolerance are associated with a proliferative hyporesponsiveness of thymocytes and peripheral T cells elicited upon TCR activation. We investigated whether these defects in tolerance induction and hyporesponsiveness of NOD T cells manifest in an altered susceptibility to TCR-induced AICD. TCR-activated NOD splenic CD4
+ and CD8
+ T cells are more resistant to AICD than control strain C57BL/6, BALB/c, and NOR T cells. NOR CD4
+ but not CD8
+ T cells are resistant to TCR-induced AICD. Whereas c-FLIP expression is reduced in activated T cells from control strains, it persists in activated NOD CD8
+ T cells and is accompanied by diminished activity of caspase-3 and -8. IL-4 reduces this c-FLIP expression and increases caspase-3 and -8 activity in activated NOD CD8
+ T cells. Moreover, IL-4 and CD28 costimulation restores the susceptibility of NOD CD8
+ T cells to AICD, and this is associated with increased expression of CD25, CD95, CD95L, and TNFR2. Thus, deficient activation of CD8
+ T cells and their greater resistance to TCR-induced AICD may mediate defective peripheral tolerance and the development of T1D in NOD mice.
Details
- Title: Subtitle
- Deficient activation and resistance to activation-induced apoptosis of cd8 + t cells is associated with defective peripheral tolerance in nonobese diabetic mice
- Creators
- Guillermo Arreaza - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaKonstantin Salojin - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaWen Yang - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaJian Zhang - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaBruce Gill - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaQing-Sheng Mi - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaJian-Xin Gao - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaCraig Meagher - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaMark Cameron - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, CanadaTerry L Delovitch - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, ON NG6 2V4, Canada
- Resource Type
- Journal article
- Publication Details
- Clinical immunology (Orlando, Fla.), Vol.107(2), pp.103-115
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S1521-6616(03)00049-4
- PMID
- 12763479
- ISSN
- 1521-6616
- eISSN
- 1521-7035
- Language
- English
- Date published
- 2003
- Academic Unit
- Pathology
- Record Identifier
- 9984047673302771
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