CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature

EBioMedicine. 2021 Dec:74:103746. doi: 10.1016/j.ebiom.2021.103746. Epub 2021 Dec 11.


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.

Keywords: Adaptive immunity; BCG; CCR6+ T cells; T cell; transcriptomics; tuberculosis; vaccine.

MeSH terms

  • Adult
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • DNA Methylation*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Humans
  • Longitudinal Studies
  • Male
  • RNA-Seq
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, CCR6 / metabolism*
  • Th1 Cells / metabolism
  • Th17 Cells / metabolism


  • BCG Vaccine
  • CCR6 protein, human
  • Receptors, Antigen, T-Cell
  • Receptors, CCR6