Cytometric detection of antigen-specific IFN-gamma/IL-2 secreting cells in the diagnosis of tuberculosis
One of the main problems in the fight against TB is the correct diagnosis of its different stages. T...
One of the main problems in the fight against TB is the correct diagnosis of its different stages. Tuberculin skin test (TST) is the most used screening method for the diagnosis of M. tuberculosis infection, even though a prior vaccination with Bacillus Calmette Gu??rin (BCG) can lead to false positive results. Other widely recognised limits of TST are the false negative tests due to immune deficiency and its inability to distinguish latently infected individuals from patients with active TB. Newer assays based on the release of interferon (IFN)-γ upon specific antigen stimulation (IGRAs) have recently become available, but their enhanced sensitivity and specificity compared to TST have not been demonstrated yet. These tests make use of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 kDa (CFP-10), i.e. proteins that are encoded within the region of difference 1 (RD1) of M. tuberculosis but not BCG genome, and thus are not synthesised by BCG substrains.
The immune response differs according to the antigen load, i.e. to active disease or latent infection. Since effector T cells (TEM) have a limited lifespan, it is possible to hypothesize that in the presence of active bacterial replication, i.e. active disease, their frequency should be increased in comparison to central memory T cells (CEM) in peripheral blood mononuclear cells (PBMC), whereas CEM should be predominant in latent infections. Beside phenotypic surface markers, memory cells can be distinguished according to their differential cytokine secretion TEM secrete IFN-γ alone while CEM secretes interleukin (IL)-2.
In this study the researchers investigated the possible contribution of active cytokine-secreting memory T cell enumeration as a diagnostic tool for TB infection and disease using a modified commercially available method. The study was conducted on peripheral blood mononuclear cells (PBMC) obtained from active TB patients, latently TB infected individuals, and healthy donors.
Results showed that IL-2 secreting cells were more frequently observed in latent TB infected individuals compared to active TB patients, suggesting that measurement of cells secreting this cytokine could be a marker of disease stage. Thus in conclusion flow cytometric cytokine-secreting cell detection technique could be considered an additional tool for TB diagnosis allowing the analysis of the immune response to M. tuberculosis-related antigens in the different stages of TB.
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