دورية أكاديمية
Constitutively active Rap1 protects from experimental autoimmune encephalomyelitis (EAE) by quantitative and qualitative modulation of auto-reactive T cells
| العنوان: | Constitutively active Rap1 protects from experimental autoimmune encephalomyelitis (EAE) by quantitative and qualitative modulation of auto-reactive T cells |
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| المؤلفون: | Franco, Salinas G, Krausz, S, Dontje, W, Tak, PP, Baeten, D, Reedquist, K |
| بيانات النشر: | British Medical Journal Publishing Group |
| سنة النشر: | 2011 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Supplement |
| الوصف: | Background and objectives Rap1 is an important signalling molecule downstream of the T-cell receptor (TCR), which can modulate T lymphocyte function upon antigen stimulation. The authors recently demonstrated that transgenic mice with constitutively active Rap1 (RapV12) are protected from experimental arthritis ( Abreu, Arthritis Rheum, 2010 ). Here, the authors aimed to identify the mechanisms of protection by using a TCR transgenic model of myelin oligodendrocyte glycoprotein (MOG)–induced experimental autoimmune encephalomyelitis (EAE) (2D2 mice). Methods Flow cytometry and ELISA were used to analyse the phenotype and cytokine profile of MOG-specific autoreactive T cells in 2D2xRapV12, 2D2, RapV12 and wild type (WT) mice (n=5 per genotype), either in basal conditions or after in vivo priming with MOG peptide. In addition, clinical EAE was monitored for 30 days (n=19 mice per genotype) Results In basal conditions, there was a strong reduction in the number of autoreactive T cells in 2D2xRapV12 versus 2D2 animals in the naïve and memory compartment (42 vs 24%, p=0.03), indicating that constitutive Rap1 activation enforces central tolerance. Qualitative analysis of the autoreactive T cells that escaped tolerance showed no differences in T cell subsets, proliferation, apoptosis, expression of costimulatory molecules and production of pro-inflammatory cytokines. After in vivo priming with MOG, however, the authors observed a profound inhibition of tumour necrosis factor production by T cells constitutively expressing Rap1 (19% of 2D2 RapV12 CD4s vs 0.4% in 2D2 controls, p=0.002), whereas there was a slight increase in IFN-γ and IL-17 production. To evaluate the pathophysiological relevance of these quantitative and qualitative alterations of the autoreactive T cells, EAE was induced in 2D2xRapV12 versus 2D2 and in RapV12 and WT littermates. In the 2D2 model, where a significant number of autoreactive T cells are still present despite the constitutive RapV12, the authors observed no difference in EAE scores but an ... |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://ard.bmj.com/cgi/content/short/70/Suppl_2/A48-bTest; http://dx.doi.org/10.1136/ard.2010.148981.16Test |
| DOI: | 10.1136/ard.2010.148981.16 |
| الإتاحة: | https://doi.org/10.1136/ard.2010.148981.16Test http://ard.bmj.com/cgi/content/short/70/Suppl_2/A48-bTest |
| حقوق: | Copyright (C) 2011, BMJ Publishing Group Ltd |
| رقم الانضمام: | edsbas.2D0F9944 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/ard.2010.148981.16 |
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