Increased T cell immunoglobulin mucin-3 and its ligand in acquired aplastic anemia

Abstract

T cell immunoglobulin mucin-3 (TIM-3) is recently described as a T helper 1 (Th)1-specific molecule, participating in the regulation of immune responses and the pathogenesis of Th1-driven diseases. The TIM-3 pathway, however, has not been investigated in acquired aplastic anemia (AA). In this study, we examined the expression of TIM-3 and interferon-γ (IFN-γ) at both transcript and protein levels in 29 acquired AA patients and in 31 controls. Increased mRNA expression of TIM-3 and IFN-γ were observed in both peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells from AA patients and controls using quantitative real-time reverse transcriptase-polymerase chain reaction. An increase of TIM-3 expression on PBMCs was detected increased in AA patients by flow cytometry. An overproduction of IFN-γ was determined in the sera from AA patients by enzyme-linked immunoassay. In addition, the expression of TIM-3 ligand, galectin-9, increased in PBMCs from AA patients. The results are the first human data to demonstrate the increase of TIM-3 expression in AA. The enhanced TIM-3 engagement by its ligand in AA patients may play an important role in the pathogenesis of this disease. © 2008 The Authors.