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.
Alves
Bryce N
BN
Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV 89557, USA. brycea@gbis.com
Marshall
Kristen
K
Tamang
David L
DL
Leong
Jeffrey
J
Redelman
Doug
D
Elliott
Viki
V
Lowe
Mark E
ME
Hudig
Dorothy
D
D000818:Animals; D045744:Cell Line, Tumor; D003089:Colipases / Q000494:pharmacology / Q000633:toxicity; D003602:Cytotoxicity, Immunologic; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D019169:Jurkat Cells; D019787:Linoleic Acid / Q000494:pharmacology / Q000633:toxicity; D008049:Lipase / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology / Q000633:toxicity; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology*; D014280:Triglycerides / Q000494:pharmacology* / Q000633:toxicity
D003089:Colipases; D011994:Recombinant Proteins; D014280:Triglycerides; D015847:Interleukin-4; D019787:Linoleic Acid; D008049:Lipase; C075988:pancreatic lipase related protein 2