Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104
| العنوان: | Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104 |
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| المؤلفون: | Rosa Medina, Daniela Santoli, Clara Brando, Tracey L. Catina, Sunil Mukhopadhyay, Eniko Kovacs, Kerry S. Campbell, Pritesh Patel |
| المصدر: | Journal of Leukocyte Biology. 78:359-371 |
| بيانات النشر: | Oxford University Press (OUP), 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Cytotoxicity, Immunologic, CD3 Complex, Lymphocyte Activation, Cell Degranulation, TNF-Related Apoptosis-Inducing Ligand, Jurkat Cells, Receptors, KIR, Neoplasms, Immunology and Allergy, Cytotoxic T cell, Receptors, Immunologic, Receptor, Membrane Glycoproteins, Ionomycin, Antibodies, Monoclonal, Receptors, KIR3DL2, U937 Cells, Natural killer T cell, Adoptive Transfer, Cell biology, Killer Cells, Natural, medicine.anatomical_structure, NK Cell Lectin-Like Receptor Subfamily K, Tumor Necrosis Factors, Receptors, Natural Killer Cell, Tetradecanoylphorbol Acetate, NK Cell Lectin-Like Receptor Subfamily C, Signal Transduction, Fas Ligand Protein, T cell, Immunology, Biology, Immediate-Early Proteins, Natural killer cell, Antigens, CD, Signaling Lymphocytic Activation Molecule Family, medicine, Humans, Monomeric GTP-Binding Proteins, Cytolytic granule, Lymphokine-activated killer cell, Ionophores, Natural Cytotoxicity Triggering Receptor 1, Tumor Necrosis Factor-alpha, Histocompatibility Antigens Class I, Cell Biology, NKG2D, Carcinogens, Apoptosis Regulatory Proteins, T-Lymphocytes, Cytotoxic |
| الوصف: | The major histocompatibility complex nonrestricted cytotoxic leukemic T cell line T acute lymphoblastic leukemia (TALL)-104 is being pursued as a therapeutic agent for cancer. However, the receptors and effector mechanisms responsible for its broad tumoricidal function remain undefined. Here, we examined the roles played by natural cytotoxicity receptors (NCR), killer cell immunoglobulin-like receptors, cytolytic granule components, and tumor necrosis factor (TNF) family members in tumor recognition and lysis by TALL-104 cells. The perforin-granzyme pathway, TNF-related apoptosis-inducing ligand (TRAIL), and Fas were each involved in the lysis of particular tumor targets by TALL-104. Furthermore, phorbol 12-myristate 13-acetate/ionomycin treatment induced surface expression of Fas-L and TRAIL. In addition, supernatants from CD3-stimulated TALL-104 cultures exhibited antiproliferative activity, which was blocked 50–90% by anti-TNF-α monoclonal antibody (mAb). Although negative for the NCR natural killer (NK)p44, this cell line was found to express NKp46. An anti-NKp46 antibody strongly blocked TALL-104-mediated lysis of certain targets and directly induced cytokine production, granule release, and redirected lysis responses. Anti-NKG2D and anti-2B4 also stimulated redirected cytotoxicity by TALL-104. By contrast, anti-NKG2A mAb did not stain the cells or inhibit killing responses. Alternatively, KIR3DL2 was detected on TALL-104, and expression of its reported ligand, human leukocyte antigen (HLA)-A, on target cells provided protection from cytotoxicity. Thus, NKp46, NKG2D, and 2B4 are activating receptors, and KIR3DL2 is an inhibitory receptor on TALL-104. The data demonstrate the ability of TALL-104 cells to recognize a wide variety of tumors with NK cell receptors and kill them with a broad arsenal of cytolytic effector mechanisms, including cytolytic granules and TNF family ligands. |
| تدمد: | 1938-3673 0741-5400 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56a8ba6383ccb0261c988159f882e890Test https://doi.org/10.1189/jlb.0604360Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....56a8ba6383ccb0261c988159f882e890 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19383673 07415400 |
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