title: Diminished response to interleukin-10 and reduced antibody-dependent cellular cytotoxicity of cord blood monocyte-derived macrophages.
abstract: Monocyte-derived macrophage (MPhi) subsets are generated by antagonistic induction pathways. A helper MPhi-type (Mh-MPhi) is induced by interferon gamma (IFN-gamma), whereas a cytotoxic MPhi-type (Mc-MPhi), induced by interleukin-10 (IL-10), is a potent mediator of antibody-dependent cellular cytotoxicity (ADCC). Compared with MPhi from healthy adults [peripheral blood monocyte-derived macrophages (PBMPhi)], cord blood MPhi (CBMPhi) were found less capable of generating Mh-MPhi. Here we tested the hypothesis that their generation of Mc-MPhi via IL-10 is also impaired. MPhi surface markers were phenotyped. IL-10 protein and mRNA production were detected after stimulation [alphaCD3 monoclonal antibody (mAb)]. CBMPhi or PBMPhi were co-cultured with MPhi-depleted mononuclear cells of adults and CD4-targeting antibodies as models for ADCC were added. In cord blood, we found diminished alphaCD3-induced IL-10 protein and mRNA production (p < 0.05 versus adults). Basal CD16 and HLA-DR expressions on CBMPhi of preterm and full-term neonates were lower (p < 0.05 versus PBMPhi). IL-10 had reduced effects on CD16 up- and HLA-DR down-modulation on CBMPhi (p < 0.05 versus PBMPhi). CD4-directed receptor modulation and deletion were reduced in the presence of CBMPhi (p < 0.05 versus PBMPhi). IL-10 failed to enhance their ADCC capacity, which was in contrast to PBMPhi (p < 0.05). These data suggest that CBMPhi have an impaired cytotoxic capacity via lower sensitivity toward IL-10.
authors.affiliation: University Children's Hospital, Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gille
authors.forename: Bärbel
authors.initials: B
authors.lastname: Spring
authors.forename: Lena J
authors.initials: LJ
authors.lastname: Tewes
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
authors.forename: Günther E
authors.initials: GE
authors.lastname: Dannecker
authors.forename: Michael K
authors.initials: MK
authors.lastname: Hoffmann
authors.forename: Martin
authors.initials: M
authors.lastname: Eichner
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
authors.forename: Thorsten W
authors.initials: TW
authors.lastname: Orlikowsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D006684:HLA-DR Antigens; D008934:Mitogens; D012333:RNA, Messenger; D017452:Receptors, IgG; D016753:Interleukin-10