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Blockade of T-cell immunoglobulin and mucin domain-containing molecule 3 aggravates T-helper cell 1 polarization in immune thrombocytopenia

Sun, Rui-Jiea,*; Hun, Shou-Yongb,*; Sui, Xiao-Huia,*; Wang, Feia; Zhang, Xiao-Meic; Liu, Xina; Li, Yinga; Shan, Ning-Ninga

Blood Coagulation & Fibrinolysis: June 2019 - Volume 30 - Issue 4 - p 133–139
doi: 10.1097/MBC.0000000000000805

An increased T-helper cell (Th) 1/Th2 ratio in the peripheral blood has been proposed to correlate with the disease activity of immune thrombocytopenia (ITP). T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is a Th1-associated cell surface molecule that regulates Th1 responses and promotes tolerance. Consequently, we aimed to determine whether the regulation of TIM-3 expression is likely to be a promising therapeutic approach for ITP. In the present study, we investigated the immunomodulatory activities of TIM-3 in human peripheral blood mononuclear cell (PBMC) cultures. Levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-4, IL-5, IL-2, and IL-10 were determined in PBMCs from 11 ITP patients and 10 healthy patients after TIM-3 antibody administration for 48 h. The proliferation of PBMCs was examined by cell counting kit-8 assay. Flow cytometry was used to observe apoptosis by staining cells with annexin V-fluorescein isothiocyanate/propidine iodide. PBMCs from ITP patients secreted higher amounts of IFN-γ than those from control patients but paradoxically expressed lower levels of TIM-3. Depletion of TIM-3 in PBMCs in vitro using a TIM-3 antibody enhanced IFN-γ secretion, directly demonstrating that TIM-3 expression on human T cells regulates proliferation and IFN-γ secretion. Failure to upregulate the T-cell expression of TIM-3 may represent a novel intrinsic defect that contributes to the pathogenesis of ITP.

aDepartment of Hematology

bDepartment of Blood Transfusion, Shandong Provincial Hospital Affiliated to Shandong University, Jinan

cDepartment of Hematology, People's Hospital of Rizhao City, Rizhao, People's Republic of China

Correspondence to Ning-Ning Shan, MD, PhD, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Rd, Jinan, Shandong 250021 E-mail:

Received 31 October, 2018

Revised 1 March, 2019

Accepted 7 April, 2019

Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.