Distinct polyfunctional CD4+ T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisy

Tuberculous pleurisy (TBP) is a frequent extrapulmonary manifestation characterized by the accumulation of inflammatory cells that can sometimes be spontaneously self-cured. To achieve a greater insight into T cells at a local site, we systematically characterized and compared the numbers of antigen-specific T cells responding to BCG- or MTB-specific antigens. Our results showed that significantly higher levels of Th1 cytokines were produced by pleural fluid cells (PFCs) than PBMCs following stimulation with BCG or peptides from Mycobacterium tuberculosis (MTB)-specific antigens, ESAT-6 and CFP-10. The proportions of Th1 cells producing IL-2 alone or IL-2 and TNF-α were higher than those producing IFN-γ alone, following stimulation with ESAT-6 or CFP-10 peptides. The cells responding to BCG, ESAT-6 and CFP-10 displayed a CD45RA(-)CCR7(-)CD62L(-)CD27(-) effector/effector memory phenotype. The percentages and median fluorescence intensity (MFI) of polyfunctional CD4(+) T cells were significantly higher following stimulation with peptides from ESAT-6 or CFP-10 than BCG. Our results demonstrated that significantly higher levels of polyfunctional CD4(+) T cells for the epitopes of ESAT-6 or CFP-10 in PFCs may play an important role in the local control of tuberculosis (TB) infection.