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

• DOI: 10.1016/j.jinf.2011.02.013
• Publication Date: 2011-03-08T04:00:21Z
• Authors: Xinjing Wang; Zhihong Cao; Jing Jiang; Yanfeng Li; Mei Dong; Mario Ostrowski; Xiaoxing Cheng
• Keywords: Adult; Male; 0303 health sciences; Membrane Proteins; Mycobacterium tuberculosis; CD8-Positive T-Lymphocytes; Middle Aged; Lymphocyte Activation; Severity of Illness Index; Up-Regulation; 3. Good health; Young Adult; 03 medical and health sciences; Humans; Female; Hepatitis A Virus Cellular Receptor 2; Tuberculosis, Pulmonary

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.