Elevated expression of Tim-3 on CD8 T cells correlates with disease severity of pulmonary tuberculosis

Abstract

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. Tim-3 expression on CD8 T cells and its influence on production of effector molecules and proliferation of CD8 T cells were examined. 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 T cells 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. The elevated expression of Tim-3 on CD8 T cells correlates with functional defects of CD8 T cells and disease severity of pulmonary TB.