The roles of multifunctional CD4 T cells in human tuberculosis are not well defined. In this study, we found that patients with tuberculosis had decreased PMA/ionomycin stimulated multifunctional CD4 T cells, and increased Mycobacterium tuberculosis antigen-specific multifunctional CD4 T cells, when compared to individuals with latent tuberculosis infection and healthy controls. PMA/ionomycin stimulated IFN-γ+IL-2+TNF-α+ CD4 T cell responses were decreased in patients with smear-positive tuberculosis compared to those with smear-negative tuberculosis. The percentage of IFN-γ+IL-2+TNF-α+ CD4 T cells in smear positive tuberculosis patients negatively correlated with the grade of sputum smear Acid-Fast Bacilli and high-resolution computed tomography score. Therefore, our findings argue against the notion that Mycobacterium tuberculosis antigen-specific multifunctional Th1 responses in peripheral blood can serve as correlates of protective immunity against tuberculosis; they suggest that the decrease in PMA/ionomycin stimulated IFN-γ+IL-2+TNF-α+ CD4 T cells may be applied for clinical diagnosis of active tuberculosis.

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Tuberculosis (TB) is currently the world's leading cause of infectious mortality. The complex immune response of the human body to Mycobacterium tuberculosis (M.tb) results in a wide array of clinical manifestations, thus the clinical and radiological diagnosis can be challenging. 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET) scan with/without computed tomography (CT) component images the whole body and provides a metabolic map of the infection, enabling clinicians to assess the disease burden. 18 F-FDG-PET/CT scan is particularly useful in detecting the disease in previously unknown sites, and allows the most appropriate site of biopsy to be selected. 18 F-FDG-PET/CT is also very valuable in assessing early disease response to therapy, and plays an important role in cases where conventional microbiological methods are unavailable and for monitoring response to therapy in cases of multidrugresistant TB or extrapulmonary TB. 18 F-FDG-PET/CT cannot reliably differentiate active TB lesion from malignant lesions and false positives can also be due to other infective or inflammatory conditions. 18 F-FDG PET is also unable to distinguish tuberculous lymphadenitis from metastatic lymph node involvement. The lack of specificity is a limitation for 18 F-FDG-PET/CT in TB management.