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Increased Number of Tc17 and Correlation with Th17 Cells in Patients with Immune Thrombocytopenia
Yu Hu1, Dao-xin Ma1*, Ning-ning Shan2, Yuan-yuan Zhu1, Xin-guang Liu1, Lei Zhang3, Shuang Yu1, Chunyan
Ji1, Ming Hou1
1 Department of Hematology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China, 2 Department of Hematology, Provincial Hospital Affiliated to
Shandong University, Jinan, People’s Republic of China, 3 Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, People’s Republic of China
Abstract
Background: IL-17-secreting CD8+ T cells (Tc17 subset) have recently been defined as a subpopulation of effector T cells implicated in the pathogenesis of autoimmune diseases. The role of Tc17 and correlation with Th17 cells in the pathophysiology of immune thrombocytopenia (ITP) remain unsettled.
Design and Methods: We studied 47 ITP patients (20 newly-diagnosed and 27 with complete response) and 34 healthy controls. IL-17-producing CD3+CD8+ cells (Tc17) and IL-17-producing CD3+CD82 cells (Th17) were evaluated by flow cytometry and expressed as a percentage of the total number of CD3+ cells. Specific anti-platelet glycoprotein (GP) GPIIb/IIIa and/or GPIb/IX autoantibodies were measured by modified monoclonal antibody specific immobilization of platelet antigens. Peripheral blood mononuclear cells of ITP patients were isolated, incubated in the presence of 0, 0.25, 0.5, or 1 mmol/L of dexamethasone for 72 h, and collected to detect Tc17 and Th17 cells by flow cytometric analysis.
Results: IL-17 was expressed on CD3+CD82 and CD3+CD8+ T cells. The percentages of Tc17 and Th17 cells in newlydiagnosed patients were significantly elevated compared to controls, and Tc17 was decreased after clinical treatment. The
Th17:Tc17 ratio was significantly lower in newly-diagnosed patients compared with controls, and was increased in patients who had complete response. There was a significantly positive correlation between Tc17 and Th17 cells in the control group, but not in the ITP patients. A positive correlation existed between Tc17 and the CD8:CD4 ratio, as well as CD8+ cells in patients with ITP. The frequencies of Tc17 were marginally higher in autoantibody-negative patients than autoantibodypositive patients. Moreover, both Tc17 and Th17 cell percentages decreased as the concentration of dexamethasone in the culture media increased in ITP patients.
Conclusions: Tc17 and the Th17 subset are involved in the immunopathology of ITP. Blocking the abnormally increased number of Tc17 may be a reasonable therapeutic strategy for ITP.
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