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Differentiation of Monocytic Cell Clones into CD8⁺ Dendritic Cells (DC) Suggests that Monocytes Can Be Direct Precursors for Both CD8⁺ and CD8^- DC in the Mouse¹

Jian-Xin Gao^*, Xingluo Liu^*, Jing Wen^*, Huiming Zhang^*, Joan Durbin, Yang Liu^2,* and Pan Zheng^2,*

^* Division of Cancer Immunology, Department of Pathology and Comprehensive Cancer Center, and Department of Pediatrics and Children’s Research Institute, Ohio State University Medical Center, Columbus, OH 43210

Dendritic cells (DC) are the professional APCs that initiate T cell immune responses. DC can develop from both myeloid and lymphoid progenitors. In the mouse, the CD8⁺ DC had been designated as "lymphoid" DC, and CD8^- DC as "myeloid" DC until recently when it was demonstrated that common myeloid progenitors can also give rise to CD8⁺ DC in bone marrow chimera mice. However, it is still not clear which committed myeloid lineages differentiate into CD8⁺ DC. Because monocytes can differentiate into DC in vivo, the simplest hypothesis is that the CD8⁺ DC can be derived from the monocyte/macrophage. In this study we show that cell clones, isolated from CD8⁺ DC lymphoma but with a monocytic phenotype (CD11c^low/-D11b^highCD8^-I-A^low), can redifferentiate into CD8⁺ DC either when stimulated by LPS and CD40L or when they migrate into the lymphoid organs. Maturation of DC in vivo correlated with strong priming of allogeneic T cells. Moreover, the monocytes from cultured splenocytes or peritoneal exudates macrophages of wild-type mice are also capable of differentiating into CD11c⁺CD8⁺ DC after their migration into the draining lymph nodes. Our results suggest that monocytes can be direct precursors for CD11c⁺CD8⁺ DC in vivo. In addition, the monocyte clones described in this study may be valuable for studying the differentiation and function of CD8⁺ DC that mediate cross-presentation of Ag to CD8 T cells specific for cell-associate Ags.

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