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Blockade of T-cell immunoglobulin and mucin domain-containing molecule 3 aggravates T-helper cell 1 polarization in immune thrombocytopenia.
- Source :
-
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis [Blood Coagul Fibrinolysis] 2019 Jun; Vol. 30 (4), pp. 133-139. - Publication Year :
- 2019
-
Abstract
- : 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.
- Subjects :
- Apoptosis
Case-Control Studies
Cell Proliferation
Cells, Cultured
Cytokines metabolism
Gene Expression Regulation
Hepatitis A Virus Cellular Receptor 2 antagonists & inhibitors
Humans
Leukocytes, Mononuclear cytology
Purpura, Thrombocytopenic, Idiopathic etiology
Purpura, Thrombocytopenic, Idiopathic metabolism
Purpura, Thrombocytopenic, Idiopathic pathology
Th1 Cells metabolism
Hepatitis A Virus Cellular Receptor 2 metabolism
Purpura, Thrombocytopenic, Idiopathic therapy
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5733
- Volume :
- 30
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
- Publication Type :
- Academic Journal
- Accession number :
- 31090595
- Full Text :
- https://doi.org/10.1097/MBC.0000000000000805