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⁺ 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⁺GZMB⁺ 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.