Pathogen-specific γδ T cell response in pediatric sepsis

Abstract

Sepsis is a leading cause of childhood mortality worldwide, with newborns and young children being at the highest risk of developing severe or lethal infections. Extensive characterization of host-pathogen interactions in early life is required to develop novel preventive and therapeutic interventions. γδ T cells are an unconventional T cell population that possess characteristics of innate and adaptive immune system. Vγ9Vδ2 T cells are a main subset of γδ T lymphocytes in human adult blood that can react in a TCR-dependent way towards phosphoantigens, small metabolites that increase upon bacterial infections. Vγ9Vδ2 T cells are also abundant in human fetal peripheral blood, but compared to their adult counterparts they have a distinct developmental origin, and are hyporesponsive towards phosphoantigens in vitro. It is not known whether Vγ9Vδ2 T cells can react towards bacterial infections in early life. In order to address this question, we investigated the response of γδ T cells in young children with blood culture-proven sepsis. By analyzing γδ TCR repertoire using high throughput sequencing, we observed that infection of young children (< 2 years) with S. aureus, but not with other pathogens, was associated with the expansion of a highly public (shared between S. aureus-infected infants) fetal-like Vγ9Vδ2 TCR repertoire. This outcome was determined to be age dependent as we did not observe this kind of expansion in children older than two years. In conclusion, our data indicate that Vγ9Vδ2 T cells can respond towards bacterial infections in early life in a pathogen-specific way.L6380075392022-05-23 <br />