Identification of a novel antigen cross-presenting cell type in spleen

Abstract

Antigen-presenting cells (APC), like dendritic cells (DC), are essential for T-cell activation, leading to immunity or tolerance. Multiple DC subsets each play a unique role in the immune response. Here, a novel splenic dendritic-like APC has been characterized in mice that has immune function and cell surface phenotype distinct from other, described DC subsets. These were identified as a cell type continuously produced in spleen long-term cultures (LTC) and have anin vivoequivalent cell type in mice, namely 'L-DC'. This study characterizes LTC-DC in terms of marker phenotype and function, and compares them with L-DC and other known splenic DC and myeloid subsets. L-DC display a myeloid dendritic-like phenotype equivalent to LTC-DC as CD11cloCD11bhiMHC-II-CD8α- cells, distinct by high accessibility and endocytic capacity for blood-borne antigen. Both LTC-DC and L-DC have strong antigen cross-presentation ability leading to strong activation of CD8+ T cells, particularly after exposure to lipopolysaccharide. However, they have weak ability to stimulate CD4+ T cells in antigen-specific responses. Evidence is presented here for a novel DC type produced byin vitrohaematopoiesis which has distinct antigen-presenting potential and reflects a DC subset present alsoin vivoin spleen.