Sepsis shapes the human γδ TCR repertoire in an age- and pathogen-dependent manner.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_AE5942648B5E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sepsis shapes the human γδ TCR repertoire in an age- and pathogen-dependent manner.
Journal
European journal of immunology
Author(s)
Giannoni E., Sanchez Sanchez G., Verdebout I., Papadopoulou M., Rezwani M., Ahmed R., Ladell K., Miners K.L., McLaren J.E., Fraser D.J., Price D.A., Eberl M., Agyeman PKA, Schlapbach L.J., Vermijlen D.
Working group(s)
Swiss Pediatric Sepsis Study
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
10/2024
Peer-reviewed
Oui
Volume
54
Number
10
Pages
e2451190
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Sepsis affects 25 million children per year globally, leading to 2.9 million deaths and substantial disability in survivors. Extensive characterization of interactions between the host and bacteria in children is required to design novel preventive and therapeutic strategies tailored to this age group. Vγ9Vδ2 T cells are the first T cells generated in humans. These cells are defined by the expression of Vγ9Vδ2 T-cell receptors (TCRs, using the TRGV9 and TRDV2 gene segments), which react strongly against the prototypical bacterial phosphoantigen HMBPP. We investigated this reactivity by analyzing the TCR δ (TRD) repertoire in the blood of 76 children (0-16 years) with blood culture-proven bacterial sepsis caused by HMBPP-positive Escherichia coli or by HMBPP-negative Staphylococcus aureus or by HMBPP-negative Streptococcus pneumoniae. Strikingly, we found that S. aureus, and to a lesser extent E. coli but not S. pneumoniae, shaped the TRDV2 repertoire in young children (<2 years) but not in older children or adults. This dichotomy was due to the selective expansion of a fetal TRDV2 repertoire. Thus, young children possess fetal-derived Vγ9Vδ2 T cells that are highly responsive toward specific bacterial pathogens.
Keywords
Humans, Receptors, Antigen, T-Cell, gamma-delta/immunology, Receptors, Antigen, T-Cell, gamma-delta/genetics, Child, Infant, Child, Preschool, Adolescent, Sepsis/immunology, Staphylococcus aureus/immunology, Streptococcus pneumoniae/immunology, Escherichia coli/immunology, Male, Female, Infant, Newborn, Age Factors, Escherichia coli Infections/immunology, Staphylococcal Infections/immunology, Neonate immunity, Sepsis, TCR, γδ T cells
Pubmed
Web of science
Open Access
Yes
Create date
05/08/2024 16:07
Last modification date
02/11/2024 7:10
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