MTB-specific lymphocyte responses are impaired in tuberculosis patients with pulmonary cavities

Objective: Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. Methods: We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTB antigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs). By flow cytometry, we then dissected CD4+ and CD8+ T lymphocytes secreting intracellular cytokines of IFN-gamma and TNF-alpha to assess the local immune response of TB patients with pulmonary cavities compared with those having other radiological infiltrates. Results: As expected, after 16 h of ex vivo activation using both ESAT-6 and CFP-10, the proportions of CD4+IFN-gamma, CD4+TNF-alpha, CD8+ TNF-alpha, and CD8+IFN-gamma cells were all markedly increased in 46 patients with TB when compared with 23 household contacts. However, the IFN-gamma and TNF-alpha responses of both CD4+ and CD8+ T lymphocytes were found to be relatively lower in 18 patients who had pulmonary cavities when compared with 28 patients who had radiological infiltrates. Moreover, patients with cavities had higher absolute numbers of neutrophils than patients with infiltrates. Further analysis indicated an inverse correlation between neutrophil counts and the proportions of IFN-gamma-secreting T cells. Conclusion: MTB-specific lymphocyte responses are impaired in TB patients with pulmonary cavities that are likely to play an important role in the pathogenesis of cavitary TB.