CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature.
EBioMedicine
; 74: 103746, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34902786
ABSTRACT
BACKGROUND:
The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity.METHODS:
We investigated immune responses in adult individuals pre and 8 months post BCG vaccination. We specifically determined changes in gene expression, cell subset composition, DNA methylome, and the TCR repertoire induced in PBMCs and CD4 memory T cells associated with antigen stimulation by either BCG or a Mycobacterium tuberculosis (Mtb)-derived peptide pool.FINDINGS:
Following BCG vaccination, we observed increased frequencies of CCR6+ CD4 T cells, which includes both Th1* (CXCR3+CCR6+) and Th17 subsets, and mucosal associated invariant T cells (MAITs). A large number of immune response genes and pathways were upregulated post BCG vaccination with similar patterns observed in both PBMCs and memory CD4 T cells, thus suggesting a substantial role for CD4 T cells in the cellular response to BCG. These upregulated genes and associated pathways were also reflected in the DNA methylome. We described both qualitative and quantitative changes in the BCG-specific TCR repertoire post vaccination, and importantly found evidence for similar TCR repertoires across different subjects.INTERPRETATION:
The immune signatures defined herein can be used to track and further characterize immune responses induced by BCG, and can serve as reference for benchmarking novel vaccination strategies.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Vacina BCG
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Receptores de Antígenos de Linfócitos T
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Linfócitos T CD4-Positivos
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Metilação de DNA
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Perfilação da Expressão Gênica
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Receptores CCR6
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article