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Institut National de la Santé et de la Recherche Médicale, Unité 437, Nantes, France and Institut de Transplantation et de Recherche en Transplantation, Nantes, France
We recently reported that splenic dendritic cells (DC) in rats can
be separated into CD4+ and CD4- subsets and
that the CD4- subset exhibited a natural cytotoxic
activity in vitro against tumor cells. Moreover, a recent report
suggests that CD4- DC could have tolerogenic properties in
vivo. In this study, we have analyzed the phenotype and in vitro T cell
stimulatory activity of freshly isolated splenic DC subsets. Unlike the
CD4- subset, CD4+ splenic DC expressed CD5,
CD90, and signal regulatory protein 
molecules. Both fresh
CD4- and CD4+ DC displayed an immature
phenotype, although CD4+ cells constitutively expressed
moderate levels of CD80. The half-life of the CD4-, but
not CD4+ DC in vitro was extremely short but cells could be
rescued from death by CD40 ligand, IL-3, or GM-CSF. The
CD4- DC produced large amounts of the proinflammatory
cytokines IL-12 and TNF- and induced Th1 responses in allogeneic
CD4+ T cells, whereas the CD4+ DC produced low
amounts of IL-12 and no TNF-, but induced Th1 and Th2 responses. As
compared with the CD4+ DC that strongly stimulated the
proliferation of purified CD8+ T cells, the
CD4- DC exhibited a poor CD8+ T cell
stimulatory capacity that was substantially increased by CD40
stimulation. Therefore, as previously shown in mice and humans, we have
identified the existence of a high IL-12-producing DC subset in the rat
that induces Th1 responses. The fact that both the CD4+ and
CD4- DC subsets produced low amounts of IFN- upon viral
infection suggests that they are not related to plasmacytoid
DC.
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