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Gordon Macpherson

Publications and source records attributed to Gordon Macpherson.

2 recordsLinked to original sources

Network of dendritic cells within the muscular layer of the mouse intestine.

Dendritic cells (DCs) are located at body surfaces such as the skin, respiratory and genital tracts, and intestine. To further analyze intestinal DCs, we adapted an epidermal sheet separation technique and obtained two intestinal layers, facing the lumen and serosa. Unexpectedly, immunolabeling of the layer toward the serosa revealed a regular, dense, planar network of cells with prominent dendritic morphology within the external muscular layer and with increasing frequency along the length of the intestine. Direct examination of the serosal-disposed layers showed a significant fraction of the DCs to express DEC-205/CD205, CD11c, Langerin/CD207, Fcgamma receptor/CD16/32, CD14, and low levels of activation markers, CD25, CD80, CD86, and CD95. By more sensitive FACS analyses, cells from this layer contained two CD11c(+) populations of CD45(+) CD205(+), CD19(-) leukocytes, MHC II(+) and MHC II(-). When ovalbumin conjugated to an anti-DEC-205 antibody was injected into mice, the conjugate targeted to these DCs, which upon isolation were able to stimulate ovalbumin-specific, CD4(+) and CD8(+) T cell antigen receptor-transgenic T cells. In vivo, these DCs responded to two microbial stimuli, systemic LPS and oral live bacteria, by up-regulating CD80, CD86, DEC-205, and Langerin within 12 h. This network of DCs thus represents a previously unrecognized antigen-presenting cell system in the intestine.

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Phenotype and function of rat dendritic cell subsets.

Dendritic cells (DC) comprise phenotypically-distinct subsets that sub-serve distinct functions in immune induction. Understanding the biology of DC subsets in vivo is crucial for the understanding of immune regulation and its perturbations in disease. This review focuses on the phenotype and functions of rat DC subsets and compares these with subsets identified in other species. Our research has concentrated on DC migrating in lymph. DC migrate constitutively from peripheral tissues to draining nodes, probably to induce/maintain tolerance to self- or harmless foreign antigens. After removal of mesenteric lymph nodes (MLN) in the rat, healing of afferent and efferent lymphatics permits migrating intestinal DC (iLDC) to be collected from the thoracic duct. We have shown that iLDC consist of least two subsets that differ in phenotype, in situ distribution and function. CD4+/SIRPalpha+ iLDC are highly immunostimulatory, but are excluded from T cell areas of MLN. In contrast, CD4-/SIRPalpha- iLDC are less potent stimulators of T cells, but carry material from apoptotic enterocytes to T cell areas of MLN. Similar subsets exist in both lymph nodes and spleen. It has been shown that phenotypically-similar subsets migrate in skin-draining lymph in cattle and sheep. We and others have shown that splenic CD4-/SIRPalpha- DC can phagocytose allogeneic cells in vitro, are poor stimulators of CD8+ T cells, and can lyse NK-sensitive target cells. Although some of our data suggest that rat CD4-/SIRPalpha- DC may equate to murine CD8+ DC, there is at present insufficient evidence to be confident of this.

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