Human γδ T cells: diverse orchestrators of the host response to influenza infection. (VIR5P.1145)

Abstract

Abstract While often mild, influenza infection can occasionally progress to severe disease and even death. It is recognized that disease progression and outcome is often worse in the young and the old; however, the reason infection progresses in some individuals and not others is still unclear. Previous findings, reported by our laboratory, from a five-year longitudinal human study have shown that a definable inflammatory cytokine signature correlates with poor clinical outcome. Moreover, we have shown that this cytokine profile correlates with inflammatory monocyte numbers. Here we show a correlation between γδ T cell numbers and inflammatory monocyte numbers during infection within this clinical cohort. Further, we show that a subset of peripheral γδ T cells exhibit a surprisingly high T cell receptor (TCR) variable region gene diversity in infected individuals. Additionally, the CDR3 TCR sequences of this cellular subset show very high diversity, while retaining repetitive VJ gene junction-determined conserved motifs. The data presented here suggest that human peripheral γδ T cells are a more diverse cellular population than previously realized and are capable of playing a pivotal role in influencing the local immune environment during influenza infection with the potential to effect long-term outcome.