title: Imbalanced expression of T-bet and T cell immunoglobulin mucin-3 in patients with aplastic anaemia.
abstract: BACKGROUND
  Activated T helper (Th)-1 CD4+ cells and their mediators are essential for pathogenesis processes in aplastic anaemia (AA). Recently, T-cell immunoglobulin and mucin domain 3 (Tim-3) molecules, a Th1-specific type 1 membrane protein, have been suggested to be important regulators of both Th1 proliferation and the development of tolerance. Moreover, T-box expressed in T cells (T-bet) is a major T cell transcription factor that regulates the expression of Th1 cytokine genes and plays a crucial role in T cell differentiation. The function of Tim-3 and its association with T-bet in the pathophysiology of AA remain unclear.
  
  
  METHODS
  Plasma IL-18, IFN-γ and IL-4 levels were measured in patients with newly diagnosed AA (n = 29), AA in remission (n = 22) and healthy subjects (n = 30) via enzyme-linked immunosorbent assay (ELISA). CD4+ Tim-3+ cells were evaluated via flow cytometry and expressed as a percentage of the total number of CD4+ cells. Using real-time quantitative polymerase chain reaction (RT-PCR) and mRNA expression analysis the expression levels of Tim-3, IL-18, IFN-γ and T-box (T-bet) were examined in all subjects.
  
  
  RESULTS
  Tim-3 was expressed on CD4+T cells. The percentages of Tim-3 cells identified in newly diagnosed patients were significantly deceased compared with the controls. Meanwhile T-bet, IL-18 and IFN-γ levels were significantly elevated in patients, which resulted in an increased ratio of T-bet/Tim-3 expression levels in patients with active disease. During the remission stages, the levels of these cytokines were comparable with those observed in the healthy controls.
  
  
  CONCLUSIONS
  These results suggest that the imbalanced expression of Tim-3 and T-bet may play a role in the pathogenesis and course of AA, and the downregulation of T-bet/Tim-3 may represent a reasonable therapeutic strategy for AA treatment.
authors: Department of Hematology, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Rd, Jinan, Shandong, 250021, People's Republic of China.
authors: Ning-ning
authors: NN
authors: Shan
authors: Yu
authors: Y
authors: Hu
authors: Xin
authors: X
authors: Liu
authors: Xin
authors: X
authors: Wang
authors: Dai
authors: D
authors: Yuan
authors: Ying
authors: Y
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology*; D002454:Cell Differentiation; D002469:Cell Separation; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058408:Th1-Th2 Balance; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor