| Autor: |
Badami, Giusto D., La Manna, Marco P., Di Carlo, Paola, Stanek, Ondrej, Linhartova, Irena, Caccamo, Nadia, Sebo, Peter, Dieli, Francesco |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 2023, p1-11, 11p |
| Abstrakt: |
Introduction: Tuberculosis (TB) remains the first cause of death from infection caused by a bacterial pathogen. Chemotherapy does not eradicate Mycobacterium tuberculosis (Mtb) fromhuman lungs, andthe pathogen causes a latent tuberculosis infectionthatcannotbepreventedbythecurrently availableBacilleCalmetteGuerin (BCG) vaccine, which is ineffective inthe prevention of pulmonary TBinadults. HLAE-restricted CD8+ T lymphocytes are essential players in protective immune responses against Mtb. Hence, expanding this population in vivo or ex vivo may be crucial for vaccination or immunotherapy against TB. Methods: The enzymatically inactive Bordetella pertussis adenylate cyclase (CyaA) toxoid is an effective tool for delivering peptide epitopes into the cytosol of antigen-presenting cells (APC) for presentation and stimulation of specific CD8+ T-cell responses. In this study, we have investigated the capacity of the CyaA toxoid to deliver Mtb epitopes known to bind HLA-E for the expansion of human CD8+ T cells in vitro. Results: Our results show that the CyaA-toxoid containing five HLA-E-restricted Mtb epitopes causes significant expansion of HLA-E-restricted antigen-specific CD8+ T cells, which produce IFN-g and exert significant cytotoxic activity towards peptide-pulsed macrophages. Discussion: HLA-E represents a promising platform for the development of new vaccines; our study indicates that the CyaA construct represents a suitable delivery system of the HLA-E-binding Mtb epitopes for ex vivo and in vitro expansion of HLA-E-restricted CD8+ T cells inducing a predominant Tc1 cytokine profile with a significant increase of IFN-γ production, for prophylactic and immunotherapeutic applications against Mtb. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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