RESUMO
Tuberculosis (TB) remains the world's leading cause of morbidity and mortality. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine currently in use, its efficacy is highly variable. It has been suggested that early antigenic presentation is a pivotal event leading to a better immune response in TB vaccine models. To investigate this further, we compared in vitro cell-mediated immune responses in the context of early sensitization with TB (i.e. healthy adults vaccinated with BCG when they were young, HD; n = 25) to those in its absence (i.e., newborns with naïve immunity to TB, UV; n = 10) by challenging mononuclear cells with BCG Moreau. After 48 hours, CD4+ and CD8+ T cells were harvested from both groups and stained for PD-1/CD25/ FOXP3. In addition, supernatants were assayed for a broad range of cytokines using an array system. The HD group showed robust reactivity to Protein Purified Derivative and BCG while the naïve, UV group did not. Similarly, in terms of PD-1 expression and Treg cells (CD4+/CD25high(+)/FOXP3+), only the HD group showed higher levels in CD4 lymphocytes. Otherwise, only the UV group showed expression of CD25dim+ as an activation marker dependent on BCG infection. In terms of cytokines, the HD group showed higher levels of Th1 (IL-2/TNF-α/IFN-γ) and regulatory (IL-10) profiles, with monocytes, but not Tr1 cells, acting as the main source of IL-10. Taken together, our results highlight critical roles of early sensitization with TB in mounting cell-mediated immune responses.
Assuntos
Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Leucócitos Mononucleares/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Brasil , Células Cultivadas , Meios de Cultura/química , Citocinas/análise , Fatores de Transcrição Forkhead/análise , Voluntários Saudáveis , Humanos , Subunidade alfa de Receptor de Interleucina-2/análise , Leucócitos Mononucleares/química , Receptor de Morte Celular Programada 1/análise , Subpopulações de Linfócitos T/química , Adulto JovemRESUMO
The Bacille Calmette-Guérin (BCG) vaccine is the only vaccine currently available for tuberculosis, and it demonstrates variable efficacy against the disease. The assessment of new vaccine strategies is hindered by the small annual probability that an infected individual will develop tuberculosis, and the lack of simple and reliable surrogate markers of protection. The frequency of cytokine-producing T cells as well as the production of IFN-γ have been disputed as surrogate markers of protection. We evaluated the evolution of these immune parameters in a population from a high burden city where BCG revaccination has been shown to result in mild protection. We found that individuals whose in vitro IFN-γ responses to mycobacterial antigens had increased by more than 3.3-fold were more likely to maintain higher responses after 1 year and to show increased expansion of IFN-γ-producing T lymphocytes than those with lower or null increase of IFN-γ.