The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

• Published in: The Journal of experimental medicine Vol. 208; no. 2; pp. 227 - 234
• Main Authors: Bigley, Venetia, Haniffa, Muzlifah, Doulatov, Sergei, Wang, Xiao-Nong, Dickinson, Rachel, McGovern, Naomi, Jardine, Laura, Pagan, Sarah, Dimmick, Ian, Chua, Ignatius, Wallis, Jonathan, Lordan, Jim, Morgan, Cliff, Kumararatne, Dinakantha S., Doffinger, Rainer, van der Burg, Mirjam, van Dongen, Jacques, Cant, Andrew, Dick, John E., Hambleton, Sophie, Collin, Matthew
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 14.02.2011
• Subjects: Adult; Antigens, CD - metabolism; Bone Marrow Cells - cytology; Brief Definitive Report; Child; Dendritic Cells - cytology; Dendritic Cells - pathology; Disease Susceptibility - etiology; Disease Susceptibility - microbiology; Disease Susceptibility - virology; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; HLA-DR Antigens - blood; Humans; Interferon-gamma - blood; Leukopenia - blood; Leukopenia - complications; Leukopenia - genetics; Microscopy, Fluorescence; Monocytes - cytology; Monocytes - pathology; Mycobacterium Infections - immunology; Syndrome
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20101459

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+CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.