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International Immunology Advance Access originally published online on March 26, 2009
International Immunology 2009 21(5):543-553; doi:10.1093/intimm/dxp026
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Hydrolysis of tumor cell lipids after CTL-mediated death

Bryce Alves1, Jeff Leong1, David L. Tamang1, Viki Elliott1, Mark Lowe2 and Dorothy Hudig1

1 Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV 89557, USA
2 Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15260, USA

Correspondence to: B. Alves; E-mail: brycea{at}gbis.com

Contributions of lipases to CTL function have been debated, including if T cell lipases damage target cells. Expression of the lipase pancreatic lipase-related protein 2 (PLRP2) was previously found in IL-4 cultured lymphocyte cell lines but absent from IL-2 cultured lymphocytes. Here, we evaluated IL-2 and IL-4 induced CTLs for hydrolysis of target cell lipids and killing. Using anti-CD3 redirected lysis of [3H]-oleic acid-labeled P815 tumor cells, we detected the release of the radioactive fatty acid (FA). When PLRP2+/+ and PLRP2–/– CTLs were compared, there was more killing by the PLRP2+/+ CTLs. However, [3H]-oleic acid release was similar per dead P815, suggesting that lipid hydrolysis was produced by the dead P815s rather than by PLRP2. The FA release and death were completely dependent on perforin and also occurred when P815s were killed by perforin-containing T cell granule extracts that lacked lipase activity. Death by the cytotoxic granules extracts was unaffected by the addition of lipases. A lipase inhibitor, tetrahydrolipstatin, blocked FA release without affecting CTL-mediated cytotoxicity. Also, CTL-mediated death caused as much FA release as death by disruption of cells by freeze–thawing. The released oleic acid may be sufficient to promote secondary apoptotic responses after CTL-induced trauma.

Keywords: fatty acid release, IL-4, lipases, pancreatic lipase-related protein 2, Tc2 lymphocytes


Transmitting editor: G. Trinchieri

Received 7 November 2008, accepted 14 February 2009.


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