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

Sepsis contributes to a major burden of disease in early life. Extensive characterization of interactions between host and bacteria in children is required to design novel preventive and therapeutic strategies tailored to this age group. Vg9Vd2 T cells are the first T cells generated in humans. These cells are defined by the expression of a Vg9Vd2 T cell receptor (TCR, using the TRGV9 and TRDV2 gene segments) on their cell surface that reacts strongly towards the prototypical bacterial-derived phosphoantigen HMBPP. Here we investigated this reactivity by analyzing in detail the TCR delta (TRD) repertoire in the blood of 76 children (0-16 years) with blood culture-proven bacterial sepsis caused by HMBPP-positive Escherichia coli (E. coli), or by HMBPP-negative Streptococcus pneumoniae (S. pneumoniae) or Staphylococcus aureus (S. aureus). Surprisingly, S. aureus, and to a lesser extent E. coli but not S. pneumoniae, strikingly shaped the TRDV2 repertoire in children younger than two years but not in older children and in adults. This shaping was due to the selective expansion of a fetal TRDV2 repertoire. Thus, young children (<2 years) possess fetal-derived Vg9Vd2 T cells that are highly responsive towards particular bacterial pathogens.