The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency.
Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR(+) lineage(-) compartment, with virtually no CD123(+) or CD11c(+) dendritic cells (DCs) and very few CD14(+) or CD16(+) monocytes. The only remaining HLA-DR(+) lineage(-) cells were circulating CD34(+) progenitor cells. Dermal CD14(+) and CD1a(+) DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR(+) peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4(+)CD25(hi)FoxP3(+) T cells, supporting a role for DC in T reg cell homeostasis.
Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, England, UK.
Venetia
V
Bigley
Muzlifah
M
Haniffa
Sergei
S
Doulatov
Xiao-Nong
XN
Wang
Rachel
R
Dickinson
Naomi
N
McGovern
Laura
L
Jardine
Sarah
S
Pagan
Ian
I
Dimmick
Ignatius
I
Chua
Jonathan
J
Wallis
Jim
J
Lordan
Cliff
C
Morgan
Dinakantha S
DS
Kumararatne
Rainer
R
Doffinger
Mirjam
M
van der Burg
Jacques
J
van Dongen
Andrew
A
Cant
John E
JE
Dick
Sophie
S
Hambleton
Matthew
M
Collin
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002648:Child; D003713:Dendritic Cells / Q000166:cytology* / Q000473:pathology; D004198:Disease Susceptibility / Q000209:etiology* / Q000382:microbiology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007970:Leukopenia / Q000097:blood / Q000150:complications / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology* / Q000473:pathology; D009164:Mycobacterium Infections / Q000276:immunology; D013577:Syndrome
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007371:Interferon-gamma
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