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The CD8 T cell‐derived lipase, pancreatic lipase related protein 2, mediates tumor killing through an indirect mechanism.
Author(s) -
Alves Bryce N.,
Tamang David Lee,
Leong Jeff,
Redelman Doug,
Lowe Mark E.,
Hudig Dorothy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.15
Subject(s) - cytotoxic t cell , cd8 , microbiology and biotechnology , t cell , lipase , chemistry , biology , immune system , enzyme , biochemistry , immunology , in vitro
What purpose could a pancreatic lipase possibly serve in cytotoxic T lymphocytes (CTLs)? Pancreatic lipase related protein 2 (PLRP2) was first identified as an IL‐4 inducible T cell protein in the early 90s. Later studies using PLRP2 knockout mice showed that PLRP2 deficient T cells have reduced lytic capacity when compared to wild type T cells, suggesting that PLRP2 may function in T cell mediated killing. Our lab has focused on the characterization of PLRP2 expression in CTLs and to determine if PLRP2 is directly or indirectly toxic to tumor cells. Expression of PLRP2 was determined over a 5 day period in the presence of IL‐4. PLRP2 mRNA expression first appeared on days 4, with increased expression by day 5. T cells grown in increasing concentrations of IL‐4 displayed a dose response in the induced expression of PLRP2 up to 250 units/ml IL‐4 (7.15x10−10M). Enrichment and depletion of both the CD4+ and CD8+ T cell populations indicated CD8+ T cells as the PLRP2 expressing subpopulation when grown in IL‐4. We tested if PLRP2 could mediate direct or indirect killing of targets using recombinant PLRP2. When rPLRP2 at 5–10ug/ml was added to tumor cells with physiological triglycerides levels, tumor viability was reduced. The tumors were refractory to PLRP2 without the triglyceride substrate. These results suggest PLRP2 may use an indirect method to mediate its toxic effect on tumors.