title: Characterization of the recognition and functional heterogeneity exhibited by cytokine-induced killer cell subsets against acute myeloid leukaemia target cell.
abstract: The polyclonal cytokine-induced killer (CIK) cells exhibit potent cytotoxicity against a variety of tumour cells including autologous and allogeneic acute myeloid leukaemic (AML) targets. At maturity, three lymphocyte subsets: CD3(-) CD56(+), CD3(+) CD56(-) and CD3(+) CD56(+), constitute the bulk of the CIK cell culture. The CD3(-) CD56(+) subset behaves like classical natural killer (NK) cells where cytotoxicity is potentiated by blocking the human leucocyte antigen Class I molecules in the AML targets. Both the CD3(+) CD56(+) and CD3(+) CD56(-) subsets, though known to kill autologous and allogeneic targets to a comparable degree and therefore non-major histocompatibility complex (MHC)-restricted, nevertheless require the presence of the MHC molecule on the target, which interacts with their CD3-T-cell receptor complex. Although CIK cells are often termed 'NK-like' T cells, we have demonstrated that the well-characterized NK receptors KIR, NKG2C/E, NKG2D and DNAM-1 are not involved in the process of AML recognition for the CD3(+) CD56(-) and CD3(+) CD56(+) subsets. The CD3(+) CD56(+) and CD3(+) CD56(-) subsets express a polyclonal and comparable TCRVbeta repertoire in a Gaussian distribution. The CD3(+) CD56(+) subset kills AML targets more efficiently than its CD3(+) CD56(-) counterpart because of the presence of a higher proportion of CD8(+) cells. The CD3(+) CD56(+) subset comprise more terminally differentiated late effector T cells that bear the CD27(+) CD28(-) or CD27(-) CD28(-) phenotype, with a higher granzyme A content. In comparison, the phenotype of the CD3(+) CD56(-) subset is consistent with early effector T cells that are CD27(+) CD28(+) and CD62L(+), known to be less cytotoxic but possess greater proliferative potential.
authors.affiliation: Department of Haematology, Singapore General Hospital, Singapore.
authors.forename: Yeh C
authors.initials: YC
authors.lastname: Linn
authors.forename: Siew Kee J
authors.initials: SK
authors.lastname: Lau
authors.forename: Bee H
authors.initials: BH
authors.lastname: Liu
authors.forename: Lee H
authors.initials: LH
authors.lastname: Ng
authors.forename: Hao X
authors.initials: HX
authors.lastname: Yong
authors.forename: Kam M
authors.initials: KM
authors.lastname: Hui
mesh_terms: D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic
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