Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection - 06/12/24
Summary |
Background |
Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the Mycobacterium tuberculosis (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.
Methods |
In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay.
Results |
ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p < 0.0001) and decreases during TB therapy (p = 0.0002). Flow cytometry confirms that ATB116-specific CD4+ T-cell response associated with Mtb regardless of infection/disease (p < 0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p = 0.016; p = 0.0242, respectively). CD4+ T cell-specific response decreases after TB therapy completion. The antigen-specific CD8+ T-cell response mirrors the CD4+ response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.
Conclusion |
We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Stage-specific antigen identification is needed for tuberculosis vaccine design. |
• | The response to a novel pool of Mtb epitopes associated with Mtb infection/disease. |
• | The response to a novel pool of Mtb epitopes decreases during the TB therapy. |
• | These results increase TB immunopathogenesis understanding and guide vaccine design. |
Keywords : Tuberculosis disease, Tuberculosis infection, TB therapy, CD4 response, IGRA, T cells, Antigen-specific response, Peptides
Plan
Vol 89 - N° 6
Article 106295- décembre 2024 Retour au numéro
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