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

• Published in: European journal of immunology Vol. 54; no. 10; pp. e2451190 - n/a
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2024
• Subjects: Adolescent; Age Factors; Bacteria; Blood culture; Cell culture; Child; Child, Preschool; Children; Escherichia coli - immunology; Escherichia coli Infections - immunology; Female; Fetuses; Humans; Infant; Infant, Newborn; Lymphocytes; Lymphocytes T; Male; Neonate immunity; Pathogens; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - immunology; Sepsis; Sepsis - immunology; Staphylococcal Infections - immunology; Staphylococcus aureus; Staphylococcus aureus - immunology; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; TCR; γδ T cells; γδ T cells; Neonate immunity; Sepsis; TCR
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.202451190

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. Using high‐throughput sequencing of the TRD repertoire of 76 children with sepsis we revealed that S. aureus (+++) and E. coli (to a lesser extent, +) but not S. pneumoniae shaped the human 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.