title: In vitro T-cell profile induced by BCG Moreau in healthy Brazilian volunteers.
abstract: 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.
authors.affiliation: a Laboratório de Imunologia Clínica; Instituto Oswaldo Cruz ; Fiocruz , Rio de Janeiro , Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Ponte
authors.forename: L
authors.initials: L
authors.lastname: Peres
authors.forename: S
authors.initials: S
authors.lastname: Marinho
authors.forename: J
authors.initials: J
authors.lastname: Lima
authors.forename: M
authors.initials: M
authors.lastname: Siqueira
authors.forename: T
authors.initials: T
authors.lastname: Pedro
authors.forename: P
authors.initials: P
authors.lastname: De Luca
authors.forename: C
authors.initials: C
authors.lastname: Cascabulho
authors.forename: L R
authors.initials: LR
authors.lastname: Castello-Branco
authors.forename: P R Z
authors.initials: PR
authors.lastname: Antas
mesh_terms: D000293:Adolescent; D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D001938:Brazil; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D051858:Forkhead Transcription Factors / Q000032:analysis; D064368:Healthy Volunteers; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D003470:Culture Media; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: BCG vaccine; BCG, bacillus calmette-guérin; CBA, cytometric beads array kit; CBMC, cord blood mononuclear cells; ELISA, enzyme-linked immunosorbent assay; ELISPOT, enzyme linked immunospot; FACS, fluorescence activating cell sorting; HD, healthy donor; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; PBMC, peripheral blood mononuclear cells; PHA, phytohaemaglutinin; PPD, protein purified derivative; TB, tuberculosis; UV, umbilical vein; cytokine; iNKT, invariant natural killer T cells; lymphocyte; phenotyping; tuberculosis