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

2011; Rockefeller University Press; Volume: 208; Issue: 2 Linguagem: Inglês

10.1084/jem.20101459

1540-9538

Venetia Bigley, Muzlifah Haniffa, Sergei Doulatov, Xiaonong Wang, Rachel Dickinson, Naomi McGovern, Laura Jardine, Sarah Pagan, Ian Dimmick, Ignatius Chua, Jonathan P. Wallis, Jim Lordan, Cliff Morgan, Dinakantha Kumararatne, Rainer Döffinger, Mirjam van der Burg, Jacques J. M. van Dongen, Andrew J. Cant, John E. Dick, Sophie Hambleton, Matthew Collin,

T-cell and B-cell Immunology

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.