PMID- 15937142 OWN - NLM STAT- MEDLINE DCOM- 20051006 LR - 20171116 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 78 IP - 2 DP - 2005 Aug TI - Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104. PG - 359-71 AB - 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-alpha 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. FAU - Brando, Clara AU - Brando C AD - The Wistar Institute, Philadelphia, PA, USA. FAU - Mukhopadhyay, Sunil AU - Mukhopadhyay S FAU - Kovacs, Eniko AU - Kovacs E FAU - Medina, Rosa AU - Medina R FAU - Patel, Pritesh AU - Patel P FAU - Catina, Tracey L AU - Catina TL FAU - Campbell, Kerry S AU - Campbell KS FAU - Santoli, Daniela AU - Santoli D LA - eng GR - 5R01 CA20833/CA/NCI NIH HHS/United States GR - CA83859/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050603 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (CD244 protein, human) RN - 0 (CD3 Complex) RN - 0 (Carcinogens) RN - 0 (FASLG protein, human) RN - 0 (Fas Ligand Protein) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Immediate-Early Proteins) RN - 0 (Ionophores) RN - 0 (KIR3DL2 protein, human) RN - 0 (KLRC1 protein, human) RN - 0 (KLRK1 protein, human) RN - 0 (Membrane Glycoproteins) RN - 0 (NCR1 protein, human) RN - 0 (NK Cell Lectin-Like Receptor Subfamily C) RN - 0 (NK Cell Lectin-Like Receptor Subfamily K) RN - 0 (Natural Cytotoxicity Triggering Receptor 1) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, KIR) RN - 0 (Receptors, KIR3DL2) RN - 0 (Receptors, Natural Killer Cell) RN - 0 (Signaling Lymphocytic Activation Molecule Family) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFSF10 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Tumor Necrosis Factors) RN - 56092-81-0 (Ionomycin) RN - EC 3.6.5.2 (GEM protein, human) RN - EC 3.6.5.2 (Monomeric GTP-Binding Proteins) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Adoptive Transfer MH - Antibodies, Monoclonal/immunology/pharmacology MH - Antigens, CD/immunology MH - Apoptosis Regulatory Proteins MH - CD3 Complex/immunology MH - Carcinogens/pharmacology MH - Cell Degranulation/immunology MH - Cytotoxicity, Immunologic/drug effects/*immunology MH - Fas Ligand Protein MH - Histocompatibility Antigens Class I/immunology MH - Humans MH - Immediate-Early Proteins/immunology MH - Ionomycin/pharmacology MH - Ionophores/pharmacology MH - Jurkat Cells MH - Killer Cells, Natural/*immunology MH - Lymphocyte Activation/drug effects/*immunology MH - Membrane Glycoproteins/immunology MH - Monomeric GTP-Binding Proteins/immunology MH - NK Cell Lectin-Like Receptor Subfamily C MH - NK Cell Lectin-Like Receptor Subfamily K MH - Natural Cytotoxicity Triggering Receptor 1 MH - Neoplasms/immunology/therapy MH - Receptors, Immunologic/immunology MH - Receptors, KIR MH - Receptors, KIR3DL2 MH - Receptors, Natural Killer Cell MH - Signal Transduction/drug effects/*immunology MH - Signaling Lymphocytic Activation Molecule Family MH - T-Lymphocytes, Cytotoxic/cytology/*immunology MH - TNF-Related Apoptosis-Inducing Ligand MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Necrosis Factor-alpha/immunology MH - Tumor Necrosis Factors/immunology MH - U937 Cells EDAT- 2005/06/07 09:00 MHDA- 2005/10/07 09:00 CRDT- 2005/06/07 09:00 PHST- 2005/06/07 09:00 [pubmed] PHST- 2005/10/07 09:00 [medline] PHST- 2005/06/07 09:00 [entrez] AID - jlb.0604360 [pii] AID - 10.1189/jlb.0604360 [doi] PST - ppublish SO - J Leukoc Biol. 2005 Aug;78(2):359-71. doi: 10.1189/jlb.0604360. Epub 2005 Jun 3.