title: Effect of interleukin-15 and Flt3-ligand on natural killer cell expansion and activation: umbilical cord vs. adult peripheral blood mononuclear cells.
abstract: Expansion and activation of cord blood (CB) natural killer (NK) cells by cytokines might greatly benefit patients undergoing stem cell transplantation by increasing resistance against viral infections and providing graft-vs.-leukemia (GVL) effects through enhanced cytolytic abilities. We tested the ability of a recently cloned stem cell factor, Flt3-ligand (Flt3L), in combination with interleukin-15 (IL-15), to stimulate CB mononuclear cells (MNCs) to proliferate and differentiate into NK cells, in comparison with adult peripheral blood (APB) MNCs. Unstimulated CB MNCs had low NK and lymphokine-activated killer (LAK) activity compared with APB MNCs. A similar dose-dependent increase in NK and LAK activity and CD16/56 expression was found with IL-15 in CB and APB MNCs after 10 days of culture. The NK cytotoxicity (against K562 cells) of IL-15-treated CB MNCs was lower than that of corresponding APB MNCs, while IL-15-induced LAK activity (against Daudi cells) of CB MNCs was comparable to that of corresponding APB MNCs. IL-15 resulted in greater CD16/56 expression in CB MNCs compared with APB MNCs after 10 days of culture. Flt3L, alone or in combination with IL-15, had little effect on CD16/56 expression and cytotoxicity. Cytotoxic activities and CD16/56 expression did not alter after CD34 depletion of CB MNCs. We therefore concluded that CB NK cells could be greatly activated and expanded with IL-15, but not with Flt3L. The greater expression of CD16/56 induced by IL-15 in CB MNCs may originate from non-CD34+ NK progenitor cells.
authors.affiliation: Department of Pediatrics, Children's Hospital, Kweishan, Taoyuan, Taiwan. alicehsu@adm.cgmh.com.tw
authors.forename: S J
authors.initials: SJ
authors.lastname: Lin
authors.forename: M H
authors.initials: MH
authors.lastname: Yang
authors.forename: H C
authors.initials: HC
authors.lastname: Chao
authors.forename: M L
authors.initials: ML
authors.lastname: Kuo
authors.forename: J L
authors.initials: JL
authors.lastname: Huang
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis; D002469:Cell Separation; D002470:Cell Survival; D005312:Fetal Blood / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000494:pharmacology*; D017452:Receptors, IgG / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; D019409:Interleukin-15; D008565:Membrane Proteins; D017452:Receptors, IgG; C084881:flt3 ligand protein