Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice
| Autor: | Esma S. Yolcu, Jerry Stein, Ayelet Kaminitz, Haval Shirwan, Nadir Askenasy, Isaac Yaniv, Enosh M. Askenasy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Interleukin 2
Programmed cell death Fas Ligand Protein Mouse Immune Cells Immunology lcsh:Medicine Autoimmunity Apoptosis chemical and pharmacologic phenomena Nod Biology T-Lymphocytes Regulatory Mice Model Organisms CD28 Antigens Mice Inbred NOD medicine Animals lcsh:Science Cells Cultured Cell Proliferation NOD mice Multidisciplinary Cell Death T Cells Effector Cell growth lcsh:R Interleukin-2 Receptor alpha Subunit Forkhead Transcription Factors hemic and immune systems Animal Models Flow Cytometry medicine.disease Mice Inbred C57BL Interleukin-2 lcsh:Q Insulitis Research Article medicine.drug |
| Zdroj: | PLoS ONE, Vol 6, Iss 6, p e21630 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-), FoxP3(-)) and suppressor (CD25(+), FoxP3(+)) CD4(+) T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4(+) subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+)CD25(-) T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis. |
| Databáze: | OpenAIRE |
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