Imbalanced expression of T-bet and T cell immunoglobulin mucin-3 in patients with aplastic anaemia.

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. DESIGN AND 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.