Introduction: Vγ9Vδ2 T cells offer promising potential for immunotherapies and could be employed to target HIV upon latency reversal. Vδ2 T cells can be expanded to great magnitudes through the application of aminobisphosphonate drugs and express multiple cytotoxic surface receptors enabling recognition of a range of self-stress molecules. Vδ2 T cell-based immunotherapies have been well tolerated in clinical trials against cancers but have achieved limited efficacy. Inducing more potent cytotoxic functions and defining mechanisms of antigen recognition may be key to improving future Vδ2 T cell-based immunotherapies against diseases such as HIV.
Methods: Using a series of redirected LDH cytotoxicity assays, we evaluated lysis of target cells by individual Vδ2 T cell surface receptors. In addition, we examined the impact of stimulation with certain combinations of cytokines during in vitro expansion on Vδ2 T cell mediated cytotoxicity.
Results: We found that Vδ2 T cells were capable of mediating lysis through NKG2D, CD16, CD3, and CD26. We also identify various cytokine combinations which were capable of enhancing Vδ2 T cell mediated cytotoxicity through a variety of these receptors.
Conclusion: We profiled Vδ2 T cell surface receptors capable of mediating direct lysis of target cells and identify several factors capable of increasing this lysis. These finding may have key implications for future Vδ2 T cell-based immunotherapies to target HIV, as many ligands for these cytotoxic surface receptors are present during infection.