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.

The role of host soluble inflammatory mediators induced by the BCG vaccine for the initiation of in vitro monocyte apoptosis in healthy Brazilian volunteers

“…TGFβ1 might act as an anti-inflammatory arm prone to damper Th1 immune response. Actually, in line with the current data, our very recent study also failed to find any Th3 cell phenotype induced by the BCG vaccine in the sensitized adult cohort: Comparable TGFβ1 levels were found regardless of the stimulus employed [ 24 ]. That study originally established that the BCG Moreau vaccine induced a significantly elevated IFN-γ/IL-10 ratio only in the HD group, confirming a polarized Th1 pattern in vitro.…”

In vitro Evidence of Human Immune Responsiveness Shows the Improved Potential of a Recombinant BCG Strain for Bladder Cancer Treatment

“…The higher production of IL-10 induced by rBCG-S1PT as compared to WT-BCG reveals a tighter control of the Th1-dependent inflammatory response, which may result in an effective induction of response in the absence of significant inflammatory side effects. Thus, the enhanced IL-10 production should be considered as a mechanism of protection against tissue injury and pathological processes associated with Th1 and inflammatory cytokines (35, 36).…”

Notes for the Immune Responses in Neonates: Commonly Expected Dampening of the Type-1 Associated Immunity during BCG Vaccination

“…Regarding the BCG vaccine, we would like to comment on our recent published data that is both important and relevant [3,4]. The ELISPOT assays performed in our studies showed that the in vitro Th-1-immune response of the umbilical cord blood (UV) was deficient related to the healthy donor adults (HD) group when cells were placed in contact with one BCG-recombinant antigen with immunodominant property, as well as a potent mitogen [3].…”