title: Human dendritic cell subsets from spleen and blood are similar in phenotype and function but modified by donor health status.
abstract: Mouse dendritic cells (DC) have been extensively studied in various tissues, especially spleen, and they comprise subsets with distinct developmental origins, surface phenotypes, and functions. Considerably less is known about human DC due to their rarity in blood and inaccessibility of other human tissues. The study of DC in human blood has revealed four subsets distinct in phenotype and function. In this study, we describe four equivalent DC subsets in human spleen obtained from deceased organ donors. We identify three conventional DC subsets characterized by surface expression of CD1b/c, CD141, and CD16, and one plasmacytoid DC subset characterized by CD304 expression. Human DC subsets in spleen were very similar to those in human blood with respect to surface phenotype, TLR and transcription factor expression, capacity to stimulate T cells, cytokine secretion, and cross-presentation of exogenous Ag. However, organ donor health status, in particular treatment with corticosteroid methylprednisolone and brain death, may affect DC phenotype and function. DC T cell stimulatory capacity was reduced but DC were qualitatively unchanged in methylprednisolone-treated deceased organ donor spleen compared with healthy donor blood. Overall, our findings indicate that human blood DC closely resemble human spleen DC. Furthermore, we confirm parallels between human and mouse DC subsets in phenotype and function, but also identify differences in transcription factor and TLR expression as well as functional properties. In particular, the hallmark functions of mouse CD8α(+) DC subsets, that is, IL-12p70 secretion and cross-presentation, are not confined to the equivalent human CD141(+) DC but are shared by CD1b/c(+) and CD16(+) DC subsets.
authors.affiliation: Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. mittag@wehi.edu.au
authors.forename: Diana
authors.initials: D
authors.lastname: Mittag
authors.forename: Anna I
authors.initials: AI
authors.lastname: Proietto
authors.forename: Thomas
authors.initials: T
authors.lastname: Loudovaris
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Mannering
authors.forename: David
authors.initials: D
authors.lastname: Vremec
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006304:Health Status; D006331:Heart Diseases / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D006684:HLA-DR Antigens; D017452:Receptors, IgG; D051193:Toll-Like Receptors; D018664:Interleukin-12