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Objectives:T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cell responses and induction of peripheral tolerance.In this study,the association of Tim-3 with active pulmonary tuberculosis (TB) was investigated.Methods:Tim-3 expression on CD8 T cells and its influence on production of effector molecules and proliferation of CD8 T cells were examined.Results:Pulmonary TB patients had significantly elevated Tim-3 expression on total CD8 T cells (P < 0.0001) and on antigen-specific CD8 T cells (P =0.0028) compared with tuberculin-positive healthy controls.The expression of Tim-3 on CD8 T cells was significantly higher in smear/ culture-positive TB patients than smear/culture-negative TB patients (P < 0.0001).Tim-3 expressing CD8 Tcells had reduced production of IFN-γ,decreased degranulation and lower proliferation in response to Mycobacterium tuberculosis antigen stimulation.Blocking of Tim-3 signaling led to significantly increased production of IFN-γ.Conclusions:The elevated expression of Tim-3 on CD8 T cells correlates with functional defects of CD8 T cells and disease severity of pulmonary TB.