Giannoni, Eric; Sanchez Sanchez, Guillem; Verdebout, Isoline; Papadopoulou, Maria; Rezwani, Moosa; Ahmed, Raya; Ladell, Kristin; Miners, Kelly L; McLaren, James E; Fraser, Donald J; Price, David A; Eberl, Matthias; Agyeman, Philipp K A; Schlapbach, Luregn J; Vermijlen, David (2024). Sepsis shapes the human γδ TCR repertoire in an age- and pathogen-dependent manner. (In Press). European journal of immunology, e2451190. Wiley 10.1002/eji.202451190
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Eur_J_Immunol_-_2024_-_Giannoni_-_Sepsis_shapes_the_human_TCR_repertoire_in_an_age__and_pathogen_dependent_manner.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (2MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine |
UniBE Contributor: |
Agyeman, Philipp Kwame Abayie |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1521-4141 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
30 Jul 2024 09:52 |
Last Modified: |
31 Jul 2024 00:17 |
Publisher DOI: |
10.1002/eji.202451190 |
PubMed ID: |
39072722 |
Uncontrolled Keywords: |
Neonate immunity Sepsis TCR γδ T cells |
BORIS DOI: |
10.48350/199371 |
URI: |
https://boris.unibe.ch/id/eprint/199371 |
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