Lipid-dependent cytotoxicity by the lipase PLRP2 and by PLRP2-positive cytotoxic T lymphocytes (CTLs)

IL‐4 induces a lipase, pancreatic lipase related protein 2 (PLRP2), in cytotoxic T lymphocytes (CTLs). Because PLRP2 in semen can mediate lipid‐dependent toxicity to sperm, we questioned whether CTL‐derived PLRP2 could support similar cytotoxicity toward tumor cells. Recombinant PLRP2 was toxic to P815 tumor cells in 48 h when lipid and another protein, colipase, were present. However, PLRP2‐positive CTLs (induced with many lots of IL‐4) were unable to mediate lipid‐dependent cytotoxicity. Notably, CTLs induced with only one lot of IL‐4 had lipid‐dependent cytotoxicity. The exceptional lot of IL‐4 was effective in multiple experiments at inducing lipid‐dependent cytotoxicity. The lipid‐dependent cytotoxicity it induced was determined to be perforin‐independent. CTLs induced with IL‐4 that was unable to induce lipid‐dependent cytotoxicity had mRNA for PLRP2 but not mRNA for colipase. Therefore, we added exogenous colipase to the CTL assays but still cytotoxicity was unchanged. We conclude (1) that lipid‐dependent cytotoxicity, promoted by the lipase PLRP2 and colipase, will kill tumor cells and (2) that more than PLRP2 alone is required for lipid‐dependent cytotoxicity mediated by CTLs. Copyright © 2009 John Wiley & Sons, Ltd.