Abstract
SummaryRelease of granulysin by γδ T cells contributes to tumour cell killing. A cytolytic 9000 MW isoform of granulysin kills tumour cells directly, whereas a 15 000 MW precursor has been hypothesized 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 with zoledronic acid or Bacillus Calmette–Guérin (BCG), or were isolated and cultured with tumour targets. Although a large proportion of resting Vδ2+ γδ T cells expressed 15 000 MW granulysin, 9000 MW 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 15 000 MW granulysin caused migration and maturation of immature DC, and also initiated fugetaxis in mature DC. Conversely, low concentrations of recombinant 15 000 MW 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.
Highlights
A small subset of T cells possess a TCR composed of γ and δ chains rather than α and β, and 20 these T cells account for up to 5% of the T cells found within human peripheral blood[1].21 While the proportion of γδ T cells in the T cell population as a whole is low, this subset does 15 not require processing and presentation of antigen to become activated, allowing a rapid23 response to infected or malignant target cells.24 Previous research has shown evidence that γδ T cells bearing a Vδ2 chain, comprising25 approximately 80% of the γδ T cell population found in the peripheral blood of humans[2], are 26 capable of recognising phosphoantigens such as prenyl pyrophosphates
Granulysin is expressed in Vδ1+ and Vδ2+ γδ T cell populations
We assessed the intracellular expression of granulysin within this cell 16 population and compared it to that observed within NK cells and CD8+ αβ T cells, previously
Summary
approximately 80% of the γδ T cell population found in the peripheral blood of humans[2], are capable of recognising phosphoantigens (pAg) such as prenyl pyrophosphates. These are 27 intermediates of isoprenoid synthesis pathways, present within both bacteria and eukaryotes. Within bacteria, the pAg (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) is produced in the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, and its eukaryotic. 31 Research has shown that Vδ2+ γδ T cells are activated by cells that accumulate HMBPP and/or. HMBPP has been found to be substantially more 35 stimulatory than IPP to Vδ2+ γδ T cells, allowing these cells to differentiate foreign
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
