Abstract

Release of granulysin by γδ T cells contributes to tumour cell killing. A cytolytic 9kDa isoform of granulysin kills tumour cells directly, while a 15kDa precursor has been hypothesised to cause both the maturation and migration of dendritic cell (DC) populations. Recruiting DC to a tumour is beneficial as these cells initiate adaptive immune responses, which contribute to the eradication of malignancies. In this study, Vδ2+ γδ T cells were activated by stimulation of peripheral blood mononuclear cells (PBMC) with zoledronic acid (ZA) or Bacillus Calmette Guérin (BCG), or were isolated and cultured with tumour targets. While a large proportion of resting Vδ2+ γδ T cells expressed 15kDa granulysin, 9kDa granulysin expression was induced only after stimulation with BCG. Increased levels of activation and granulysin secretion were also observed when Vδ2+ γδ T cells were cultured with the human B cell lymphoma line Daudi. High concentrations of recombinant 15kDa granulysin caused migration and maturation of immature DC, and also initiated fugetaxis in mature DC. Conversely, low concentrations of recombinant 15kDa granulysin resulted in migration of mature DC, but not immature DC. Our data therefore support the hypothesis that Vδ2+ γδ T cells can release granulysin, which may modulate recruitment of DC, initiating adaptive immune responses.