PMID- 12724286 OWN - NLM STAT- MEDLINE DCOM- 20040406 LR - 20171116 IS - 0006-3363 (Print) IS - 0006-3363 (Linking) VI - 69 IP - 2 DP - 2003 Aug TI - Human choriocarcinoma cell resistance to natural killer lysis due to defective triggering of natural killer cells. PG - 627-33 AB - 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. FAU - Avril, Tony AU - Avril T AD - EA 3249 Cellules hematopoietiques, hemostase et greffe, Faculte de Medecine, Tours, France. FAU - Iochmann, Sophie AU - Iochmann S FAU - Brand, Denys AU - Brand D FAU - Bardos, Pierre AU - Bardos P FAU - Watier, Herve AU - Watier H FAU - Thibault, Gilles AU - Thibault G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030430 PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (CD2 Antigens) RN - 0 (CD244 protein, human) RN - 0 (CD48 Antigen) RN - 0 (CD48 protein, human) RN - 0 (DNA, Complementary) RN - 0 (Fc gamma receptor IIA) RN - 0 (Membrane Glycoproteins) RN - 0 (Phytohemagglutinins) RN - 0 (Receptors, IgG) RN - 0 (Receptors, Immunologic) RN - 0 (Signaling Lymphocytic Activation Molecule Family) SB - IM MH - Antibodies, Monoclonal/pharmacology MH - Antibody-Dependent Cell Cytotoxicity/physiology MH - Antigens, CD/biosynthesis/genetics MH - CD2 Antigens/genetics MH - CD48 Antigen MH - Cell Line, Tumor MH - Choriocarcinoma/*pathology MH - Cytotoxicity, Immunologic MH - DNA, Complementary/genetics MH - Fluorescent Antibody Technique MH - Humans MH - Killer Cells, Natural/*physiology MH - Membrane Glycoproteins/genetics MH - Phytohemagglutinins/pharmacology MH - Receptors, IgG/genetics MH - Receptors, Immunologic/genetics MH - Signaling Lymphocytic Activation Molecule Family MH - Transfection EDAT- 2003/05/02 05:00 MHDA- 2004/04/07 05:00 CRDT- 2003/05/02 05:00 PHST- 2003/05/02 05:00 [pubmed] PHST- 2004/04/07 05:00 [medline] PHST- 2003/05/02 05:00 [entrez] AID - biolreprod.102.009290 [pii] AID - 10.1095/biolreprod.102.009290 [doi] PST - ppublish SO - Biol Reprod. 2003 Aug;69(2):627-33. doi: 10.1095/biolreprod.102.009290. Epub 2003 Apr 30.