Journal article
CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature
EBioMedicine, Vol.74, Art. 103746
2021
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.
Details
- Title
- CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature
- Authors/Creators
- A. Singhania (Author/Creator) - La Jolla Institute for ImmunologyP. Dubelko (Author/Creator) - La Jolla Institute for ImmunologyR. Kuan (Author/Creator) - La Jolla Institute for ImmunologyW.D. Chronister (Author/Creator) - La Jolla Institute for ImmunologyK. Muskat (Author/Creator) - La Jolla Institute for ImmunologyJ. Das (Author/Creator) - Linköping UniversityE.J. Phillips (Author/Creator) - Vanderbilt UniversityS.A. Mallal (Author/Creator) - Vanderbilt UniversityG. Seumois (Author/Creator) - La Jolla Institute for ImmunologyP. Vijayanand (Author/Creator) - La Jolla Institute for ImmunologyA. Sette (Author/Creator) - La Jolla Institute for ImmunologyM. Lerm (Author/Creator) - Linköping UniversityB. Peters (Author/Creator) - La Jolla Institute for ImmunologyC. Lindestam Arlehamn (Author/Creator)
- Publication Details
- EBioMedicine, Vol.74, Art. 103746
- Publisher
- Elsevier B.V.
- Identifiers
- 991005543753607891
- Copyright
- © 2021 The Author(s).
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.194 Tuberculosis & Leprosy
- 1.194.273 TB Diagnostics & Treatment
- Web Of Science research areas
- Medicine, Research & Experimental
- ESI research areas
- Clinical Medicine