Selective developmental defects of cord blood antigen-presenting cell subsets.
Defective antigen-presenting cell (APC) function has been hypothesized to contribute to increased infection susceptibility in newborns. We used multiparameter flow cytometry to characterize APC subsets in adult peripheral blood (APB) and cord blood (CB). APB had a higher proportion of CD11c+ dendritic cells (DC), whereas CB mainly contained CD123+ DC. APB was enriched in CD16+CD11c+ DC subset, whereas CD34+CD11c-CD123lo cells were prominent in CB. Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production was dampened in myeloid DC and monocytes from CB, whereas IL-1alpha production was not different. The reduction in TNF-alpha response did not appear to result from reduced surface detection of LPS, because CD14, toll-like receptor (TLR)-4 and TLR-2 levels were not reduced in CB APC compared with APB cells. Also, there was no correlation between TLR-2 or TLR-4 levels and TNF-alpha production in myeloid DC and monocytes. CB monocytes had lower surface HLA-DR immediately ex vivo. Both APB and CB monocytes upregulated HLA-DR after incubation, but an additional LPS-induced increase in HLA-DR was suggested only in APB monocytes. APB monocytes also showed a greater LPS-induced increase in CD40 expression. Together, our data show significant, selective differences in circulating APC between neonates and adults.
Drohan
Laura
L
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5164, USA.
Harding
James J
JJ
Holm
Bari
B
Cordoba-Tongson
Eileen
E
Dekker
Cornelia L
CL
Holmes
Tyson
T
Maecker
Holden
H
Mellins
Elizabeth D
ED
D000328:Adult; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D019013:CD40 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors