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The effect of interleukin (IL)‐21 and CD4+CD25++ T cells on cytokine production of CD4+ responder T cells in patients with myasthenia gravis
Authors:M. Alahgholi‐Hajibehzad  H. Durmuş  F. Aysal  Y. Gülşen‐Parman  P. Oflazer  F. Deymeer  G. Saruhan‐Direskeneli
Affiliation:1. Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey;2. Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran;3. Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey;4. Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey
Abstract:Impairment of the suppressive function of regulatory T (Treg) cells has been reported in myasthenia gravis (MG). In this study, cytokine‐related mechanisms that may lead to the defect of Treg were investigated in patients with anti‐acetylcholine receptor antibody‐positive MG (AChR + MG). Proliferation and cytokine production of responder T (Tresp) cells in response to polyclonal activation were measured in a suppression assay. The effect of interleukin (IL)‐21 on suppression was evaluated in vitro in co‐culture. IL‐21 increased the proliferation of Tresp cells in Tresp/Treg co‐cultures. Tresp cells from patients with MG secreted significantly lower levels of IL‐2. In patients with MG, IL‐2 levels did not change with the addition of Treg to cultures, whereas it decreased significantly in controls. In Tresp/Treg co‐cultures, IL‐4, IL‐6 and IL‐10 production increased in the presence of Treg in patients. Interferon (IFN)‐γ was decreased, whereas IL‐17A was increased in both patient and control groups. IL‐21 inhibited the secretion of IL‐4 in MG and healthy controls (HC), and IL‐17A in HC only. The results demonstrated that IL‐21 enhances the proliferation of Tresp cells in the presence of Treg. An effect of IL‐21 mainly on Tresp cells through IL‐2 is implicated.
Keywords:cytokine  IL‐21  myasthenia gravis  Treg
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