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.

B lymphocyte, CD1 antigen, CD123 antigen, CD14 antigen, CD16 antigen, CD34 antibody, CD4 antigen, HLA DR antigen, Langerhans cell, NK T cell lymphoma, T cell depletion, T lymphocyte, article, blood disease, bone marrow, colony forming unit GM, controlled study, dendritic cell, glycoprotein p 15095, granulocyte precursor, hematopoiesis, homeostasis, human, human cell, human tissue, lymphoid progenitor cell, macrophage, monocyte, monocytopenia, priority journal, protein tyrosine kinase, t6 antigen
dx.doi.org/10.1084/jem.20101459, hdl.handle.net/1765/23336
The Journal of Experimental Medicine
Erasmus MC: University Medical Center Rotterdam

Bigley, V, Haniffa, M, Doulatov, S, Wang, X.N, Dickinson, R, McGovern, N, … Collin, M. (2011). The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. The Journal of Experimental Medicine, 208(2), 227–234. doi:10.1084/jem.20101459