Phenotype and function of rat dendritic cell subsets

Abstract

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.