title: Human hematopoietic CD34+ progenitor cells induce natural killer cell alloresponses via NKG2D activation.
abstract: Human CD34+ cells cross-interact with allogeneic T lymphocytes. In this study we addressed the interaction between CD34+ cells and allogeneic natural killer (NK) cells. Purified NK cells were cultured with allogeneic KIR-permissive CD34+ or CD14+ blood cells, obtained from HLA group C homozygous donors, or with high-dose interleukin-2. A cytotoxicity assay was used to test the ability of NK cells to lyse NK-sensitive K562 or NK-resistant Daudi cells. Cytofluorometric assays were employed to assess cell phenotype and cytokine release. CD34+ cells induced greater lysis of K562 (p = 0.02) and Daudi cells (p = 0.01) than monocytes. CD34 cell stimulation resulted in upregulation of CD69 and CD25 on NK cells and in the production of interferon γ and tumor necrosis factor α. NK activation by CD34+ cells was inhibited by an anti-NKG2D antibody. However, NKG2D ligands such as MIC (MHC class I chain)-A/B and ULBP (UL16 binding protein)-1/3 were not detected on CD34+ cells. Cross-talk between NK and CD34+ cells also induced the upregulation of CD40 and CD86 co-stimulatory molecules on CD34+ cells. Our study indicates a direct NKG2D-dependent stimulatory effect of human CD34+ cells on allogeneic NK cells. These findings may be relevant to the NK-mediated rejection effect in HLA-mismatched hematopoietic stem cell transplantation.
authors.affiliation: Institute of Hematology and Medical Oncology "L.&A. Seragnoli," University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ulbar
authors.affiliation: Institute of Hematology and Medical Oncology "L.&A. Seragnoli," University of Bologna, Bologna, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nicolini
authors.affiliation: Institute of Hematology and Medical Oncology "L.&A. Seragnoli," University of Bologna, Bologna, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Chirumbolo
authors.affiliation: Institute of Hematology and Medical Oncology "L.&A. Seragnoli," University of Bologna, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tolomelli
authors.affiliation: Institute for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinle
authors.affiliation: Section of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL; University of Illinois at Chicago Cancer Center, University of Illinois at Chicago, Chicago, IL.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rondelli
authors.affiliation: Institute of Hematology and Medical Oncology "L.&A. Seragnoli," University of Bologna, Bologna, Italy. Electronic address: mario.arpinati@unibo.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Arpinati
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D013234:Stem Cells / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K