title: Mutual interaction between human multipotent adult progenitor cells and NK cells.
abstract: Human multipotent adult progenitor cells (hMAPCs) are isolated from bone marrow with a more extensive expansion capacity compared to human mesenchymal stem cells (hMSCs) and with the ability to differentiate into endothelium. Like hMSCs, hMAPCs inhibit T-cell proliferation induced by alloantigens. In this study, we tested the interaction between hMAPCs and natural killer (NK) cells. We assessed the susceptibility of hMAPCs to NK cell-mediated lysis and the immunomodulation of hMAPCs on NK cell function during IL-2-driven stimulation and the cytolytic effector phase. Human MAPCs express the ligands PVR and ULBP-2/5/6, which are recognized by activating NK cell receptors. However, they also express MHC class I molecules, which induce inhibitory signals in NK cells. Freshly isolated NK cells at different effector:target ratios did not kill hMAPCs as assessed by an MTT and (51)Cr-release assay, while hMAPCs impaired the cytotoxic activity of resting NK cells against the NK-sensitive K562 leukemia cell line. By contrast, IL-2-stimulated NK cells were capable of killing hMAPCs, and preactivated NK cells were not influenced during their cytotoxic effector function against K562 cells by hMAPCs. When added during the 6-day preactivation phase with IL-2, hMAPCs dose-dependently reduced NK cell proliferation in an IDO-dependent manner, but they did not influence the induction of cytotoxic capacity by IL-2. This study indicates that human MAPCs mutually interact with NK cells.
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Pediatric Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Jacobs
authors.forename: Jeroen
authors.initials: J
authors.lastname: Plessers
authors.forename: Jef
authors.initials: J
authors.lastname: Pinxteren
authors.forename: Valerie D
authors.initials: VD
authors.lastname: Roobrouck
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Stefaan W
authors.initials: SW
authors.lastname: Van Gool
mesh_terms: D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
chemical_list: D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011994:Recombinant Proteins; D007371:Interferon-gamma