کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3201673 | 1201959 | 2007 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Defective T-cell activation caused by impairment of the TNF receptor 2 costimulatory pathway in common variable immunodeficiency Defective T-cell activation caused by impairment of the TNF receptor 2 costimulatory pathway in common variable immunodeficiency](/preview/png/3201673.png)
BackgroundPatients with common variable immunodeficiency have defective T-cell activation after stimulation via T-cell receptor (TCR)/CD28 or by recall antigens.ObjectiveIn the current study, we investigated whether TNF–receptor 2 (RII) costimulation, which is important for sufficient TCR/CD28 stimulation, was significantly impaired in common variable immunodeficiency (CVID).MethodsWe studied T-cell activation events such as CD69 induction, calcium flux through store operated calcium channels, protein kinase C-θ translocation, and costimulation via TNF-RII compared with costimulation via CD28.ResultsBy measuring TNF receptor–associated factor 1 expression, which is induced by TCR alone and can be upregulated by either CD28 or TNF-RII costimulation, we show that costimulation via CD28 is intact, whereas costimulation via TNF-RII in these patients is impaired. The ras-activation pathway as tested by CD69 induction, calcium flux through store operated calcium channels, and protein kinase C-θ translocation were comparable in CVID and control T cells.ConclusionTaken together, these data indicate that the primary TCR signal as well as the signal derived from CD28 are normal but that TNF-RII–supported TCR costimulation is defective, most likely leading to impairment of an important amplification loop, such as TNF-RII augmented nuclear factor-κB activation.Clinical implicationsThe finding of defective TNF-RII cosignaling in patients with CVID may help to define the activation pathway affected, thus potentially leading to a characterization of the molecular defect and molecular diagnosis in at least some of these patients.
Journal: Journal of Allergy and Clinical Immunology - Volume 120, Issue 5, November 2007, Pages 1193–1200