The effect of interleukin (IL)-21 and CD4+CD25++ T cells on cytokine production of CD4+ responder T cells in patients with myasthenia gravis

Abstract

Impairment of the suppressive function of regulatory T (T ) cells has been reported in myasthenia gravis (MG). In this study, cytokine-related mechanisms that may lead to the defect of T were investigated in patients with anti-acetylcholine receptor antibody-positive MG (AChR + MG). Proliferation and cytokine production of responder T (T ) 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 T cells in T /T co-cultures. T 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 T to cultures, whereas it decreased significantly in controls. In T /T co-cultures, IL-4, IL-6 and IL-10 production increased in the presence of T 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 T cells in the presence of T . An effect of IL-21 mainly on T cells through IL-2 is implicated.

Chinese Herbal Medicine for Myasthenia Gravis: A Systematic Review and Meta-Analysis

“…It was suggested that IL-10 and IL-4 were acting on the antigen-presenting cell to inhibit cytokine production by Th1 cells and also can inhibit antigen presentation of macrophages ( Chen et al, 2016 ). In addition, IL-4 and IL-10 production increased in the presence of Treg in MG patients ( Alahgholi-Hajibehzad et al, 2017 ).…”

Decreased regulatory function of CD4+CD25+CD45RA+ T cells and impaired IL‐2 signalling pathway in patients with type 2 diabetes mellitus

“…Isolated Tresp cells were re‐suspended in PBS (2 × 10 6 cells/mL) and labelled/incubated with carboxyfluorescein diacetate succinimidyl ester (CFSE, final concentration: 2 μmol/L; Sigma, Cat no: 21888) for 12 minutes at 37°C . After a final washing process, labelled Tresp (1 × 10 5 cells/well) were cultured in 96‐well flat bottom plates (Jet Biofil, Shanghai, China, Cat no: TCP001096) and stimulated with plate bound anti‐CD3 (clone: OKT3, Biolegend, San Diego, CA, USA, Cat no: 317326) and soluble anti‐CD28 (clone: 28.2, Biolegend, San Diego, CA, USA, Cat no: 302933) in the presence/absence of isolated Treg cells.…”

Imbalance of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells in adult patients with primary immune thrombocytopenia

“…4 Tfh cells can mediate the occurrence and development of autoimmune diseases by secreting IL-21 and regulating antibody production by B cells. [5][6][7] Under normal circumstances, the antibodies produced by the GC (germinal center) reaction can precisely target foreign pathogens, limiting autoimmunity and excessive inflammation. If the Tfh-mediated B-cell reaction is too strong and excessive antibodies are produced, the autoimmune diseases, chronic diseases, inflammation, allergic reactions, or B-cell-related tumors may be induced.…”

“…If the Tfh-mediated B-cell reaction is too strong and excessive antibodies are produced, the autoimmune diseases, chronic diseases, inflammation, allergic reactions, or B-cell-related tumors may be induced. 6,8 Studies have shown that in children and adult ITP patients, 9,10 the proportion of Tfh cells is increased significantly, but little is known about the causes of excessive activation of Tfh cells. Therefore, negative regulation in GC is also very important.…”