The elevated expression of LAG-3 on CD8+T cells correlates with disease severity of pulmonary TB

Lymphocyte-activation gene 3 (LAG-3) plays an important role in regulating T-cell responses and inducing peripheral tolerance. Our aim in this study was to investigate the relationship between LAG-3 and active tuberculosis (ATB) and the impact of LAG-3 blockade on CD8⁺T cells.

Flow cytometry was used to detect the expression of LAG-3 on CD4⁺T and CD8⁺T cells in the peripheral blood and bronchoalveolar lavage fluid from ATB patients and to explore the relationship between LAG-3 and ATB.

The expression of LAG-3 on CD4⁺T and CD8⁺T cells in ATB patients was increased (P < 0.001), and CD8⁺T cells with high expression of LAG-3 were associated with sputum culture results (P < 0.05). We further analyzed the relationship between the expression of LAG-3 in CD8⁺T cells and the severity of tuberculosis and found that the expression of LAG-3 on CD8⁺T cells in smear-positive tuberculosis patients was significantly higher than that in sputum smear-negative tuberculosis patients (P < 0.05). LAG-3 expression on CD8⁺T cells was negatively correlated with the presence of lung lesions (P < 0.05). After stimulation with a tuberculosis-specific antigen, the expression of LAG-3 on tuberculosis-specific CD8⁺T cells was also upregulated, and LAG-3-expressing CD8⁺T cells showed reduced production of IFN-γ, decreased activation, and lower proliferation, while the function of CD8⁺T cells was restored when LAG-3 signaling was blocked.

This study further explored the relationship between immune exhaustion caused by LAG-3 and immune escape of Mycobacterium tuberculosis and revealed that the elevated expression of LAG-3 on CD8⁺T cells correlates with functional defects of CD8⁺T cells and the severity of pulmonary TB.