Abstract
BackgroundT cells producing multiple factors have been shown to be required for protection from disease progression in HIV but we have recently shown this not to be the case in TB. Subjects with active disease had a greater proportion of polyfunctional cells responding to ESAT-6/CFP-10 stimulation than their infected but non-diseased household contacts (HHC). We therefore wanted to assess this profile in subjects who had successfully completed standard TB chemotherapy.MethodsWe performed a cross-sectional study using PBMC from TB cases (pre- and post-treatment) and HHC. Samples were stimulated overnight with TB antigens (ESAT-6/CFP-10 and PPD) and their CD4+ and CD8+ T cells were assessed for production of CD107a, IFN-γ, IL-2 and TNF-α and the complexity of the responses was determined using SPICE and PESTLE software.Results and ConclusionsWe found that an increase in complexity (i.e., production of more than 1 factor simultaneously) of the T cell profile was associated with TB disease and that this was significantly reduced following TB treatment. This implies that T cells are able to respond adequately to TB antigens with active disease (at least initially) but the ability of this response to protect the host from disease progression is hampered, presumably due to immune evasion strategies by the bacteria. These findings have implications for the development of new diagnostics and vaccine strategies.
Highlights
Tuberculosis (TB) is a global health problem with 2 billion people infected with the causative agent Mycobacterium tuberculosis (MTb)
Production of CD107a, IFN-c, IL-2 or TNF-a by T cells following MTb antigen-specific T cells is increased in TB cases at recruitment but comparable to household contacts (HHC) posttreatment
The proportion of CD4+ or CD8+ cells positive for any one factor following PHA stimulation was significantly increased in TB cases before treatment compared to both HHC and cases following treatment (p,0.01 and p,0.05 respectively; Table 1) indicating that cells from TB cases prior to treatment are more responsive to general stimulation
Summary
Tuberculosis (TB) is a global health problem with 2 billion people infected with the causative agent Mycobacterium tuberculosis (MTb). IFN-c producing CD4+ T cells provide the major effector response to TB but while IFN-c is required for protection against disease progression in TB it is not sufficient on its own [2]. T cells that produce multiple factors simultaneously are termed polyfunctional T cells (PFT) and have been shown to provide protection against disease progression in HIV-1 infection [4] and vaccine induced immunity [5]. We have recently shown that this same profile of response to Tuberculosis (TB) antigens is higher in patients with active disease compared to latent infection following stimulation with ESAT-6/CFP-10 [6] suggesting this phenotype is not protective in the TB setting. T cells producing multiple factors have been shown to be required for protection from disease progression in HIV but we have recently shown this not to be the case in TB. We wanted to assess this profile in subjects who had successfully completed standard TB chemotherapy
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