title: Lower concentrations of methyl-β-cyclodextrin combined with interleukin-2 can preferentially induce activation and proliferation of natural killer cells in human peripheral blood.
abstract: Previous studies have demonstrated that high concentrations of methyl-β-cyclodextrin (MβCD, 10-15 mM) can interfere with the formation of lipid rafts and inhibit activation of lymphocytes. In this report, we determined that lower concentrations of MβCD (1-4 mM) could accelerate the proliferation of lymphocytes in human peripheral blood mononuclear cells (PBMCs). In the expanded cells, CD3(-)CD56(+) natural killer (NK) cells were the dominant subpopulation, and a significant dose-effect relationship existed between the proportion of NK cells and the concentration of MβCD. In the groups treated with 3-4 mM MβCD, the proportions of NK cells reached a level of more than 60%. When PBMCs were treated with MβCD, CD69 was more preferentially expressed on CD3(-)CD56(+) cells than on CD3(+) cells at 48 and 72 hours. The expression of CD25 had no distinct difference at 48 hours, but when recombinant human interleukin-2 (IL-2) was added for a further 24 hours, it was also preferentially expressed on NK cells. MβCD and IL-2 synergistically could also induce interferon-γ (IFN-γ) production in CD56(+) human PBMCs. Mechanistic studies revealed that IFN-γ production in response to MβCD plus IL-2 was IL-12 independent but depended on endogenous IL-18 and IL-1β, and CD56(+)CD14(+) dendritic cell-like cells and B cells might mediate the ability of MβCD to activate NK cells. The MβCD-activated NK cells also had high cytotoxicity against the natural killer cell-sensitive K562 cells or lymphokine-activated killer cell-sensitive DAUDI cells in vitro. These studies indicated that lower concentrations of MβCD combined with IL-2 can preferentially induce activation and proliferation of NK cells in PBMCs.
authors.affiliation: Central Laboratory of the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233003, People's Republic of China.
authors.forename: He-Zuo
authors.initials: HZ
authors.lastname: Lü
authors.forename: An-You
authors.initials: AY
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Bai-Qing
authors.initials: BQ
authors.lastname: Li
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D020382:Interleukin-18; D053583:Interleukin-1beta; D007376:Interleukin-2; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D018664:Interleukin-12; D007371:Interferon-gamma