Triglyceride lipids can enhance the cytotoxicity of induced cytotoxic T lymphocytes (CTLs) (83.8)

Abstract

Abstract IL-4 induces pancreatic lipase related protein 2 (PLRP2) in cytotoxic T lymphocytes (CTLs). Because PLRP2 in semen mediates lipid-dependent toxicity to sperm, we questioned whether CTL-derived PLRP2 could support similar cytotoxicity towards tumor cells. First we tested recombinant PLRP2. Microgram/ml concentrations were toxic to P815 cells in 48 hr assays when lipid and co-lipase were present. Next we found that CTLs secrete triglyceride lipase but that most IL-2 or IL-4 induced CTLs were unable to mediate lipid-dependent cytotoxicity. A single, exceptional lot of IL-4 reproducibly induced lipid-dependent cytotoxicity that was also perforin-independent. In efforts to induce the lipid-dependent CTL killing again, attempts were made to block type 1-polarizing cytokines, including biasing the T cells cultures with more IL-4 or with IL-12 blocking antibodies, and using T cells without IFN-ã receptors. These attempts were unsuccessful at inducing triglyceride-enhanced cytotoxicity. The CTLs induced with IL-4 consistently had mRNA for PLRP2 but lacked mRNA for co-lipase. Therefore, we added exogenous co-lipase to the cytotoxicity assays. Cytotoxicity was unaltered. We conclude (1) that lipid-dependent cytotoxicity by PLRP needs co-lipase and (2) that more than PLRP2 is required for lipid-dependent cytotoxicity by CTLs. Supported by NIH R01CA38942 and T32CA09563.