Abstract
BackgroundThe spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named ‘L-DC’ was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. That study also redefined splenic eosinophils as well as resident and inflammatory monocytes in spleen.ResultsL-DC are shown to be distinct from known splenic macrophages and monocyte subsets. Using a new flow cytometric procedure, it has been possible to identify and isolate L-DC in order to assess their functional competence and ability to activate T cells both in vivo and in vitro. L-DC are readily accessible to antigen given intravenously through receptor-mediated endocytosis. They are also capable of CD8+ T cell activation through antigen cross presentation, with subsequent induction of cytotoxic effector T cells. L-DC are MHCII− cells and unable to activate CD4+ T cells, a property which clearly distinguishes them from conventional DC. The myeloid subsets of resident monocytes, inflammatory monocytes, neutrophils and eosinophils, were found to have varying capacities to take up antigen, but were uniformly unable to activate either CD4+ T cells or CD8+ T cells.ConclusionThe results presented here demonstrate that L-DC in spleen are distinct from other myeloid cells in that they can process antigen for CD8+ T cell activation and induction of cytotoxic effector function, while both L-DC and myeloid subsets remain unable to activate CD4+ T cells. The L-DC subset in spleen is therefore distinct as an antigen presenting cell.
Highlights
The spleen is an important site for hematopoiesis
Conventional dendritic cell (DC) were gated as CD11chiMHCII+ cells, further delineated to give CD8+ cDC and CD8− cDC on the basis of CD8 and CD11b expression (Table 1)
Myeloid cells were initially gated as CD11bhiCD11c− cells, further delineated to give neutrophils, inflammatory monocytes and eosinophils on the basis of Ly6C, Ly6G and Siglec-F expression (Table 1)
Summary
The spleen is an important site for hematopoiesis It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. A novel dendritic-like cell type in spleen named ‘L-DC’ was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. The spleen is important for myelopoiesis, and myeloid cells are primarily located within the red pulp region. Multiple subsets of dendritic cells (DC) have been described in spleen, located mainly within the. Monocytes develop in bone marrow from a common myeloid/dendritic cell progenitor [4, 5], and continuously migrate into blood and spleen as mature cells [6]. When monocytes enter tissues they terminally differentiate to give macrophages, recent evidence suggests that blood precursors may not be the only source of tissue macrophages, with evidence that they can derive from endogenous progenitors of yolk sac and embryonic origin [7,8,9]
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