Abstract
Important advances have been made in the immunodiagnosis of tuberculosis (TB) based on the detection of Mycobacterium tuberculosis (MTB)-specific T cells. However, the sensitivity and specificity of the immunological approach are relatively low because there are no specific markers for antigen-specific Th cells, and some of the Th cells that do not produce cytokines can be overlooked using this approach. In this study, we found that MTB-specific peptides of ESAT-6/CFP-10 can stimulate the expression of CD40L specifically in CD4+ T cells but not other cells from pleural fluid cells (PFCs) in patients with tuberculous pleurisy (TBP). CD4+CD40L+ but not CD4+CD40L− T cells express IFN-γ, IL-2, TNF-α, IL-17 or IL-22 after stimulation with MTB-specific peptides. In addition, CD4+CD40L+ T cells were found to be mostly polyfunctional T cells that simultaneously produce IFN-γ, IL-2 and TNF-α and display an effector or effector memory phenotype (CD45RA−CD45RO+CCR7−CD62L−ICOS−). To determine the specificity of CD4+CD40L+ T cells, we incubated PFCs with ESTA-6/CFP-10 peptides and sorted live CD4+CD40L+ and CD4+CD40L− T cells by flow cytometry. We further demonstrated that sorted CD4+CD40L+, but not CD4+CD40L− fractions, principally produced IFN-γ, IL-2, TNF-α, IL-17 and IL-22 following restimulation with ESTA-6/CFP-10 peptides. Taken together, our data indicate that the expression of CD40L on MTB-specific CD4+ T cells could be a good marker for the evaluation and isolation of MTB-specific Th cells and might also be useful in the diagnosis of TB.
Highlights
Tuberculous pleurisy (TBP)—the second most frequent manifestation of extrapulmonary tuberculosis (TB) after lymph node TB—is restricted to the pleural cavity, which contains numerous immunocompetent cells [1]
Pleural fluid cells (PFCs) from tuberculous pleurisy (TBP) or Peripheral blood mononuclear cells (PBMCs) from healthy individuals were stimulated in the presence or absence of Mycobacterium tuberculosis (MTB)-specific peptides (ESAT-6/CFP-10)
We found that unstimulated cells do not express CD40L
Summary
Tuberculous pleurisy (TBP)—the second most frequent manifestation of extrapulmonary tuberculosis (TB) after lymph node TB—is restricted to the pleural cavity, which contains numerous immunocompetent cells [1]. Some studies have shown that IL-4 is not essential for the development of a protective immune response to MTB [5,6], Sugawara et al showed that IL-4 is required for proper defense against TB infection [7]. Th17 cells can recruit granulocytes to the site of MTB persistence to produce inflammation [8]; these cells seem to play an important role in the early development of protective immunity in the lungs [8,9,10]. IL-22-producing CD4+ T cells are distinct from Th1 and Th17 cells and have been shown to play important roles in the human immune response to mycobacteria [11]
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