Identification of Mycobacterium tuberculosis-Specific Th1, Th17 and Th22 Cells Using the Expression of CD40L in Tuberculous Pleurisy

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

Comparison of immunological status of African and European cord blood mononuclear cells.

Item does not contain fulltextThe cellular aspects of the immunologic development of the fetus during pregnancy have been studied mainly in populations living in economically well developed countries, and there is no data concerning variation of the neonatal cellular immune system in geographically distinct areas with different environments. Here, we report a comparative immunologic marker analysis of the circulating mononuclear cell subsets in unstimulated cord blood of newborns from Gabon and Austria, assessing the activation and maturation status of T and B lymphocytes as well as antigen-presenting cells. Cells and markers hypothesized to be modulated by frequent exposure to microorganisms and parasites such as regulatory T cells and the expression of toll-like receptor 2 on antigen-presenting cells were also studied. We found marked differences in terms of expression of immunologic markers between the two populations, pointing to a comparatively enhanced maturation status of the neonatal immune system in general in the African setting. The observations suggest that environmental factors, including differential exposure to pathogens as well as nutritional differences, may have substantial impact on the development of the fetal immune system