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Singhania A, Dubelko P, Kuan R, et al. CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature. EBioMedicine. 2021;74:103746doi: 10.1016/j.ebiom.2021.103746.
Singhania, A., Dubelko, P., Kuan, R., Chronister, W. D., Muskat, K., Das, J., Phillips, E. J., Mallal, S. A., Seumois, G., Vijayanand, P., Sette, A., Lerm, M., Peters, B., & Lindestam Arlehamn, C. (2021). CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature. EBioMedicine, 74103746. https://doi.org/10.1016/j.ebiom.2021.103746
Singhania, Akul, et al. "CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature." EBioMedicine vol. 74 (2021): 103746. doi: https://doi.org/10.1016/j.ebiom.2021.103746
Singhania A, Dubelko P, Kuan R, Chronister WD, Muskat K, Das J, Phillips EJ, Mallal SA, Seumois G, Vijayanand P, Sette A, Lerm M, Peters B, Lindestam Arlehamn C. CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature. EBioMedicine. 2021 Dec 10;74:103746. doi: 10.1016/j.ebiom.2021.103746. Epub 2021 Dec 10. PMID: 34902786.
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EBioMedicine. 2021 Dec 10;74:103746. doi: 10.1016/j.ebiom.2021.103746. Epub 2021 Dec 10.

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

EBioMedicine

Akul Singhania, Paige Dubelko, Rebecca Kuan, William D Chronister, Kaylin Muskat, Jyotirmoy Das, Elizabeth J Phillips, Simon A Mallal, Grégory Seumois, Pandurangan Vijayanand, Alessandro Sette, Maria Lerm, Bjoern Peters, Cecilia Lindestam Arlehamn

Affiliations

  1. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  2. Division of Infection and Inflammation, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
  3. Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA 6150, Australia; Vanderbilt University School of Medicine, Nashville, TN 37235, USA.
  4. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  5. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA. Electronic address: [email protected].

PMID: 34902786 DOI: 10.1016/j.ebiom.2021.103746

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.

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

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

Conflict of interest statement

Declaration of Competing Interest The authors declare no competing interests, except for Dr. Phillips who reports grants from NHMRC Australia, grants from NIH, personal fees from Uptodate/Lexicomp, pe

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