title: Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity.
abstract: CD3(+)CD56(+) cytokine-induced killer (CIK) cells display a potent cytolytic activity. The adhesion molecule lymphocyte function-associated antigen-1 plays a crucial role in binding as well as in cytolytic activity of CIK cells against tumor target cells expressing the corresponding ligands. CIK cells express activating natural killer (NK) receptors, including NKG2D, DNAX accessory molecule-1 (DNAM-1), and low levels of NKp30. Cell signaling not only through TCR/CD3 but also through NKG2D, DNAM-1, and NKp30 leads to CIK cell activation resulting in granule exocytosis, cytokine secretion, and cytotoxicity. Antibody blocking experiments showed that DNAM-1, NKG2D, and NKp30 are involved in the TCR-independent tumor cell recognition and killing. Anti-CMV-specific CIK cells could be expanded in standard CIK cultures and mediate both specific, MHC-restricted recognition and TCR-independent NK-like cytolytic activity against leukemic cell lines or fresh leukemic blasts. Antibody blocking of lymphocyte function-associated antigen-1 and DNAM-1 led to significant reduction of both CTL and NK-cell functions, whereas blocking of NKG2D and NKp30 only inhibited NK-like cytotoxicity. Their dual-effector function suggests that CIK cells, when used in a clinical setting, may control both neoplastic relapses and viral infections, 2 frequently associated complications in patients who received a transplant.
authors.affiliation: Laboratory of Cellular Therapy G. Lanzani, USC Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Pievani
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Borleri
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Josée
authors.initials: J
authors.lastname: Golay
authors.forename: Martino
authors.initials: M
authors.lastname: Introna
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D017252:CD3 Complex; D019002:CD56 Antigen; C527085:KLRK1 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; C431710:NCR3 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3