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

Area of Science:

• Immunology
• Pediatrics
• Microbiology

Background:

• Sepsis poses a significant global threat to children, causing millions of deaths and disabilities annually.
• Understanding host-bacterial interactions in pediatric sepsis is crucial for developing targeted interventions.
• Vγ9Vδ2 T cells, the earliest T cells in humans, recognize bacterial phosphoantigens.

Purpose of the Study:

• To investigate the Vγ9Vδ2 T-cell receptor (TCR) repertoire in children with bacterial sepsis.
• To determine how different bacterial species influence the TCR repertoire in various age groups.
• To explore the role of fetal-derived T cells in pediatric sepsis immunity.

Main Methods:

• Analysis of the T-cell receptor delta (TRD) repertoire in the blood of 76 children (0-16 years) with bacterial sepsis.
• Categorization of sepsis based on causative bacteria: HMBPP-positive Escherichia coli, HMBPP-negative Staphylococcus aureus, or HMBPP-negative Streptococcus pneumoniae.
• Comparison of TRDV2 repertoire patterns between young children (<2 years), older children, and adults.

Main Results:

• Staphylococcus aureus and, to a lesser extent, Escherichia coli significantly shaped the TRDV2 repertoire in young children (<2 years).
• This effect was not observed in older children or adults, indicating an age-specific immune response.
• The observed dichotomy was attributed to the selective expansion of a fetal-derived TRDV2 repertoire in infants.

Conclusions:

• Young children possess a fetal-derived Vγ9Vδ2 T-cell repertoire that exhibits heightened responsiveness to specific bacterial pathogens like S. aureus.
• This finding highlights a unique immunological characteristic of early childhood that influences sepsis outcomes.
• Targeting this fetal-derived T-cell response may offer novel therapeutic avenues for pediatric bacterial sepsis.