Subject(s)
Choriocarcinoma/immunology , Cytotoxicity, Immunologic/physiology , HLA Antigens/physiology , Histocompatibility Antigens Class I/physiology , Killer Cells, Natural/physiology , Lectins, C-Type , Antibodies/pharmacology , Antigens, CD/immunology , Choriocarcinoma/pathology , Cytotoxicity, Immunologic/drug effects , HLA-G Antigens , Histocompatibility Antigens Class I/immunology , Interleukin-2/pharmacology , Killer Cells, Lymphokine-Activated/physiology , Lymphocytes/drug effects , Lymphocytes/physiology , Membrane Glycoproteins/immunology , NK Cell Lectin-Like Receptor Subfamily D , Tumor Cells, CulturedABSTRACT
The lack of classical HLA molecules on trophoblast prevents allorecognition by maternal T lymphocytes, but poses the problem of susceptibility to NK lysis. Expression of the nonclassical class I molecule, HLA-G, on cytotrophoblast may provide the protective effect. However, the class I-negative syncytiotrophoblast escapes NK lysis by maternal PBL. In addition, while HLA-G-expressing transfectants of LCL.721.221 cells are protected from lymphokine-activated killer lysis, extravillous cytotrophoblast cells and HLA-G-expressing choriocarcinoma cells (CC) are not. The aim of this work was therefore to clarify the role of HLA class I expression on trophoblast cell resistance to NK lysis and on their susceptibility to lymphokine-activated killer lysis. Our results showed that both JAR (HLA class I-negative) and JEG-3 (HLA-G- and HLA-Cw4-positive) cells were resistant to NK lysis by PBL and were equally lysed by IL-2-stimulated PBL isolated from a given donor. In agreement, down-regulating HLA class I expression on JEG-3 cells by acid treatment, masking these molecules or the putative HLA-G (or HLA-E) receptor CD94/NKG2 and the CD158a/p58.1 NKR with mAbs, and inducing self class I molecule expression on JAR cells did not affect NK or LAK lysis of CC. These results demonstrate that the resistance of CC to NK lysis mainly involves an HLA class I-independent mechanism(s). In addition, we show that the expression of a classical class I target molecule (HLA-B7) on JAR cells is insufficient to induce lysis by allospecific polyclonal CTL.
Subject(s)
Cytotoxicity, Immunologic , Histocompatibility Antigens Class I/immunology , Killer Cells, Natural/immunology , Lectins, C-Type , Trophoblasts/immunology , Antigens, CD/immunology , Cell Line , Citric Acid/pharmacology , HLA Antigens/immunology , HLA-C Antigens/immunology , HLA-G Antigens , Humans , Killer Cells, Lymphokine-Activated/immunology , Membrane Glycoproteins/immunology , NK Cell Lectin-Like Receptor Subfamily C , NK Cell Lectin-Like Receptor Subfamily D , Receptors, Immunologic/immunology , Receptors, KIR , Receptors, KIR2DL1 , Receptors, KIR2DL3 , Receptors, Natural Killer Cell , Trophoblasts/drug effectsABSTRACT
During pregnancy, important modifications of hemostasis occur resulting in mothers in hypercoagulability and the role of placental cells such as trophoblast cells has been hypothesized. In this study, we first showed that syncytiotrophoblast plasma membranes, isolated from normal human placenta, expressed a strong tissue factor (TF) activity. We then studied TF activity of two continuous trophoblast cell lines (JEG-3 and BeWo) in comparison to human umbilical vein endothelial cells (HUVEC) and transformed human endothelial cells (ECV-304). TF assays were performed on intact detached confluent cells. Unstimulated JEG-3 and BeWo cells exhibited a very high TF activity which slightly increased after 2 to 4 h TNF-alpha stimulation. In contrast, HUVEC and ECV-304 had a lower basal TF activity which was mainly inducible by TNF-alpha, with a maximum effect after 4 to 6 h stimulation. For both cell types, TF activity was decreased to basal value after 16-hour TNF-alpha stimulation. These results support that trophoblast cells are able to express TF but the involvement of this property in the hemostatic physiological changes observed during pregnancy, remains to be demonstrated.
Subject(s)
Cell Membrane/chemistry , Choriocarcinoma/chemistry , Neoplasm Proteins/analysis , Pregnancy/blood , Thromboplastin/analysis , Trophoblasts/chemistry , Uterine Neoplasms/chemistry , Cell Line, Transformed/drug effects , Cells, Cultured/drug effects , Choriocarcinoma/pathology , Cycloheximide/pharmacology , Dactinomycin/pharmacology , Endothelium, Vascular/chemistry , Endothelium, Vascular/drug effects , Female , Gene Expression Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Thromboplastin/biosynthesis , Thromboplastin/genetics , Tumor Cells, Cultured/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Umbilical Veins , Uterine Neoplasms/pathologyABSTRACT
Choriocarcinoma cells (CC) in vitro are resistant to NK lysis but sensitive to lysis by blood or decidual effectors activated by interleukin-2 (IL-2). Because lytic activity requires a step of adhesion, the adhesive properties of the choriocarcinoma cells BeWo, JEG-3, and JAR were examined functionally toward peripheral blood lymphocytes. The adhesion of lymphocytes to choriocarcinoma cells was very low and did not increase after stimulating lymphocytes with IL-2. As demonstrated by cytofluorimetry analysis, choriocarcinoma cells and cytotrophoblast cells prepared from term placenta expressed intercellular adhesion molecule-1 (ICAM-1), whereas only CC expressed CD56. Tumor necrosis factor-alpha or interferon-gamma increased the expression of ICAM-1 on choriocarcinoma cells without modifying the adhesion of lymphocytes to choriocarcinoma cells. These results suggest that resistance of choriocarcinoma cells to lysis by cytotoxic effectors could partially be attributed to the low level of lymphocyte adhesion to these cells.