Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccine
Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active tuberculosis (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors to control TB, early after infection, the innate immune response must play a role in tackling the disease. Here, we performed in-depth analyses of the acute immune response to MTBVAC, a candidate vaccine engineered from Mtb with the aim of protecting adults from pulmonary TB disease, still a major global challenge. scRNA-seq shows expansion of CD4<sup>+</sup> and cytotoxic γδ T-cells, data confirmed by flow cytometry. CD4 T-cells exhibited lower HLA-DR and higher L-selectin expression, compared to BCG-stimulation, indicating differential activation or dynamics. Importantly, MTBVAC-activated γδ T-cells had a unique cytotoxic CD16<sup>+</sup>GZMB<sup>+</sup> phenotype, reminiscent of effector cells found in Mtb positive individuals controlling infection. IFN-γ and TNF-α were released in cultures, while IL-17A/F were almost undetectable.
Authors
- Eugenia Puentes
- Mar Valés‐Gómez (ORCID: https://orcid.org/0000-0001-7424-3206)
- Ana Dopazo (ORCID: https://orcid.org/0000-0002-4910-1684)
- Nacho Aguiló (ORCID: https://orcid.org/0000-0001-7897-9173)
- Enrique Vázquez (ORCID: https://orcid.org/0000-0003-1157-2592)
- Álvaro F. García-Jiménez (ORCID: https://orcid.org/0000-0002-9182-5168)
- Ingrid Murillo
- Hugh T. Reyburn (ORCID: https://orcid.org/0000-0003-2855-1595)
- Alberto Benguría (ORCID: https://orcid.org/0000-0002-5536-566X)
- Gloria Esteso (ORCID: https://orcid.org/0000-0001-6162-013X)
- Esteban Rodríguez (ORCID: https://orcid.org/0000-0003-3277-6682)
- Carlos Martı́n (ORCID: https://orcid.org/0000-0003-2993-5478)
- María-José Felgueres
Institutions
- Consejo Superior de Investigaciones Científicas (ES)
- Universidad de Zaragoza (ES)
- Instituto de Salud Carlos III (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES)
- Centro Nacional de Biotecnología (ES)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1038/s41541-025-01110-3
- Citations
- 3
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- “la Caixa” Foundation
- Universidad Autónoma de Madrid
- European Regional Development Fund
- Agencia Estatal de Investigación
- European Social Fund