Diminished response to interleukin-10 and reduced antibody-dependent cellular cytotoxicity of cord blood monocyte-derived macrophages

Monocyte-derived macrophage (M(D) subsets are generated by antagonistic induction pathways. A helper M(D-type (Mh-M Phi) is induced by interferon gamma (IFN-gamma), whereas a cytotoxic M(D-type (Mc-M Phi), induced by interleukin-10 (IL-10), is a potent mediator of antibody-dependent cellular cytotoxicity (ADCC). Compared with M Phi from healthy adults [peripheral blood monocyte-derived macrophages (PBM Phi], cord blood M Phi (CBM Phi) were found less capable of generating Mh-M Phi. Here we tested the hypothesis that their generation of Mc-M Phi via IL-10 is also impaired. M(P surface markers were phenotyped. IL-10 protein and mRNA production were detected after stimulation [alpha CD3 monoclonal antibody (mAb)]. CBM Phi or PBM Phi were co-cultured with M Phi-depleted mononuclear cells of adults and CD4-targeting antibodies as models for ADCC were added. In cord blood, we found diminished alpha CD3-induced IL-10 protein and mRNA production (p < 0.05 versus adults). Basal CD16 and HLA-DR expressions on CBM Phi of preterm and full-term neonates were lower (p < 0.05 versus PBM Phi). IL-10 had reduced effects on CD 16 up- and HLA-DR down-modulation on CBM Phi (p < 0.05 versus PBM Phi). CD4-directed receptor modulation and deletion were reduced in the presence of CBM Phi (p < 0.05 versus PBM Phi). IL-10 failed to enhance their ADCC capacity, which was in contrast to PBM Phi (p < 0.05). These data suggest that CBM(D have an impaired cytotoxic capacity via lower sensitivity toward IL- 10.