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1 August 2003 Human Choriocarcinoma Cell Resistance to Natural Killer Lysis Due to Defective Triggering of Natural Killer Cells
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Abstract

The trophoblast, the outermost layer of the human placenta, lacks expression of the classical human leukocyte antigen (HLA) class I molecules. This prevents allorecognition by T cells but raises the question of what protects the trophoblast from natural killer (NK) cells. In a previous study, we have shown that choriocarcinoma cell (CC) resistance to NK lysis was mainly independent of HLA class I molecules. In the present study, we postulated that CC may prevent activation of NK cells by failing to stimulate their triggering receptors (TR). To test this hypothesis, we evaluated the lysis of JAR and JEG-3 CC after effective cross-linking and activation of NK cells by means of lectins or antibodies. Our results show that NK-resistant CC were sensitive to lysis by unstimulated peripheral blood lymphocytes in the presence of phytohemagglutin (PHA), to antibody-dependent cell cytotoxicity in presence of anti-Tja antibodies, and to monoclonal antibody redirected killing using anti-TR antibodies anti-CD16 and anti-CD244/2B4. Finally, CC fail to express CD48, the ligand for CD244/2B4. These results indicate that the resistance of CC to lysis results primarily from defective NK cell activation, at least partially due to the lack of expression of ligands, such as CD48, involved in the triggering of NK cells.

Tony Avril, Sophie Iochmann, Denys Brand, Pierre Bardos, Hervé Watier, and Gilles Thibault "Human Choriocarcinoma Cell Resistance to Natural Killer Lysis Due to Defective Triggering of Natural Killer Cells," Biology of Reproduction 69(2), 627-633, (1 August 2003). https://doi.org/10.1095/biolreprod.102.009290
Received: 15 July 2002; Accepted: 1 April 2003; Published: 1 August 2003
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