title: A CD2 high-expressing stress-resistant human plasmacytoid dendritic-cell subset.
abstract: Human plasmacytoid dendritic cells (pDCs) were considered to be a phenotypically and functionally homogeneous cell population; however, recent analyses indicate potential heterogeneity. This is of major interest, given their importance in the induction of anti-viral responses and their role in creating immunologically permissive environments for human malignancies. For this reason, we investigated the possible presence of human pDC subsets in blood and bone marrow, using unbiased cell phenotype clustering and functional studies. This defined two major functionally distinct human pDC subsets, distinguished by differential expression of CD2. The CD2(hi) and CD2(lo) pDCs represent discontinuous subsets, each with hallmark pDC functionality, including interferon-alpha production. The rarer CD2(hi) pDC subset demonstrated a significant survival advantage over CD2(lo) pDC during stress and upon exposure to glucocorticoids (GCs), which was associated with higher expression of the anti-apoptotic molecule BCL2. The differential sensitivity of these two human pDC subsets to GCs is demonstrated in vivo by a relative increase in CD2(hi) pDC in multiple myeloma patients treated with GCs. Hence, the selective apoptosis of CD2(lo) pDC during stress represents a novel mechanism for the control of innate responses.
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.|Concord Clinical School, University of Sydney, Sydney, NSW, Australia.|Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Bryant
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.|Concord Clinical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Fromm
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Kupresanin
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.|Concord Clinical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Georgina
authors.initials: G
authors.lastname: Clark
authors.affiliation: Concord Clinical School, University of Sydney, Sydney, NSW, Australia.|Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
authors.forename: Candice
authors.initials: C
authors.lastname: Clarke
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.|Concord Clinical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Silveira
authors.affiliation: Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Hayley
authors.initials: H
authors.lastname: Suen
authors.affiliation: Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Brown
authors.affiliation: Department of Haematology, Concord Hospital, Sydney, NSW, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Newman
authors.affiliation: Department of Haematology, Concord Hospital, Sydney, NSW, Australia.
authors.forename: Ilona
authors.initials: I
authors.lastname: Cunningham
authors.affiliation: Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: P Joy
authors.initials: PJ
authors.lastname: Ho
authors.affiliation: Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.|Blood and Bone Marrow Transplant Service, Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bradstock
authors.affiliation: Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Douglas
authors.initials: D
authors.lastname: Joshua
authors.affiliation: Dendritic Cell Research, ANZAC Research Institute, Concord Repatriation General Hospital, Sydney, NSW, Australia.|Concord Clinical School, University of Sydney, Sydney, NSW, Australia.|Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.|Department of Haematology, Concord Hospital, Sydney, NSW, Australia.
authors.forename: Derek Nj
authors.initials: DNj
authors.lastname: Hart
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D018801:CD2 Antigens; D005938:Glucocorticoids; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors