title: Suppression of natural killer cells in the presence of CD34+ blood progenitor cells and peripheral blood lymphocytes.
abstract: Abstract Mobilization of CD34 + peripheral blood progenitor cells (PBPCs) with granulocyte-colony stimulating factor (G-CSF) may induce functional alterations in peripheral blood lymphocyte (PBL) subsets. We and others have shown that natural killer (NK) cells from PBPC collections are less expandable in vitro than those obtained during steady-state hematopoiesis. We show here that the extent of this proliferation deficit is related to the number of circulating CD34 + cells in vivo at the time of PBPC apheresis. Likewise, addition of autologous CD34 + cells to unseparated PBL reduced the expansion of the NK-cell subset by 22.2% +/- 6.0% (n = 10; P <.005). In contrast, when using purified NK cells, their proliferation remained unimpaired by autologous CD34 + cells. Supernatants from CD34 + cells cultured with autologous PBLs had an inhibitory effect on proliferation of purified NK cells (n = 16; P =.03), indicating that an interaction between CD34 + cells and lymphocytes is essential for the suppressive effect on NK cells. To investigate the role of T cells in this interaction, intracellular cytokines were determined in T cells cultured for 7 days with or without autologous CD34 + cells. When cultured with CD34 + cells, the frequency of IL-2-producing CD4 + and CD8 + T cells was reduced by 19% and 24%, respectively, compared with T cells cultured alone (n = 7; P =.016). Interferon-gamma-producing T cells were slightly reduced ( P = not statistically significant [ns]). Finally, the influence of T cells and NK cells on the recovery of myeloid colony-forming cells (CFU-GMs) from purified CD34 + cells was examined. In the presence of T cells, 16% +/- 6% of the input CFU-GM recovered after 7 days, compared with 5% +/- 4% in the presence of NK cells (n = 5; P = ns). Our findings point to an inhibition of NK-cell proliferation mediated by an interaction of CD34 + cells and T cells occurring during PBPC mobilization with G-CSF.
authors.affiliation: Laboratory of Tumor Biology & Angiogenesis, Division of Hematology & Oncology, Department of Internal Medicine, University Hospital, Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Clausen
authors.forename: M
authors.initials: M
authors.lastname: Enk
authors.forename: B
authors.initials: B
authors.lastname: Vergeiner
authors.forename: K
authors.initials: K
authors.lastname: Eisendle
authors.forename: A L
authors.initials: AL
authors.lastname: Petzer
authors.forename: G
authors.initials: G
authors.lastname: Gastl
authors.forename: E
authors.initials: E
authors.lastname: Gunsilius
mesh_terms: D018952:Antigens, CD34; D001773:Blood Cells; D001943:Breast Neoplasms / Q000628:therapy; D016022:Case-Control Studies; D002450:Cell Communication; D049109:Cell Proliferation; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D008223:Lymphoma / Q000628:therapy; D008297:Male
chemical_list: D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor