Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation

Abstract

Animal models of hematopoietic stem cell transplantation have been used to analyze the turnover of bone marrow–derived cells and to demonstrate the critical role of recipient antigen-presenting cells (APC) in graft versus host disease (GVHD). In humans, the phenotype and lineage relationships of myeloid-derived tissue APC remain incompletely understood. It has also been proposed that the risk of acute GVHD, which extends over many months, is related to the protracted survival of certain recipient APC. Human dermis contains three principal subsets of CD45+HLA-DR+ cells: CD1a+CD14− DC, CD1a−CD14+ DC, and CD1a−CD14+FXIIIa+ macrophages. In vitro, each subset has characteristic properties. After transplantation, both CD1a+ and CD14+ DC are rapidly depleted and replaced by donor cells, but recipient macrophages can be found in GVHD lesions and may persist for many months. Macrophages isolated from normal dermis secrete proinflammatory cytokines. Although they stimulate little proliferation of naive or memory CD4+ T cells, macrophages induce cytokine expression in memory CD4+ T cells and activation and proliferation of CD8+ T cells. These observations suggest that dermal macrophages and DC are from distinct lineages and that persistent recipient macrophages, although unlikely to initiate alloreactivity, may contribute to GVHD by sustaining the responses of previously activated T cells.

Intradermal application of vitamin D3 increases migration of CD14+dermal dendritic cells and promotes the development of Foxp3+regulatory T cells

“…Whereas human LCs seem to specialize in inducing cytotoxic CD8 + T cell responses, 37,38 human CD1a + DDCs, which constitute most of DDCs, mediate CD4 + T cell responses, 39 while CD14 + DDCs are proposed to promote antibody production by B cells through the induction of follicular helper T cells. 40 Compared with other crawl-out DC types, the CD14 + DDC subset expresses lower levels of the DC co-stimulatory molecules CD80 and CD86 and the DC maturation marker CD83, [41][42][43] which was also observed in this study. This maturation profile was accompanied by a lower T cell stimulatory capacity in comparison to other skin DC subsets, 40,41 which may be a reflection of the tolerogenic nature of this CD14 + DDC subset.…”

Normal Bone Deposition Occurs in Mice Deficient in Factor XIII-A and Transglutaminase 2

“…Antibody AC-1A1 has been widely used to detect FXIII-A in cells and tissues by immunohistochemistry and immunofluorescence analysis [8,[17][18][19][20]. While we have confirmed that mAb AC-1A1 preferentially recognises FXIII-A positive cells in sections of embedded mouse heart, it strongly cross-reacts with off-target antigens in cultured cells, and so appears unsuitable for defining the subcellular trafficking of FXIII-A.…”

Recent insights into cutaneous immunization: How to vaccinate via the skin

“…In human skin, three additional langerin-negative subsets of DCs have been identified, referred to as CD1a+, CD14+ and CD141 hi DCs [72][73][74]. Several studies have highlighted the potential of the different DCs subsets in influencing the direction of the immune response with the CD14+ DC subset being shown to preferentially induce a Th1-biased response [14,75] and to promote the secretion of large amounts of different immunoglobulins [14,76].…”