Differentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC) suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8 alpha- DC in the mouse.
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 CD8alpha(+) DC had been designated as "lymphoid" DC, and CD8alpha(-) DC as "myeloid" DC until recently when it was demonstrated that common myeloid progenitors can also give rise to CD8alpha(+) DC in bone marrow chimera mice. However, it is still not clear which committed myeloid lineages differentiate into CD8alpha(+) DC. Because monocytes can differentiate into DC in vivo, the simplest hypothesis is that the CD8alpha(+) DC can be derived from the monocyte/macrophage. In this study we show that cell clones, isolated from CD8alpha(+) DC lymphoma but with a monocytic phenotype (CD11c(low/-)D11b(high)CD8alpha(-)I-A(low)), can redifferentiate into CD8alpha(+) 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(+)CD8alpha(+) DC after their migration into the draining lymph nodes. Our results suggest that monocytes can be direct precursors for CD11c(+)CD8alpha(+) DC in vivo. In addition, the monocyte clones described in this study may be valuable for studying the differentiation and function of CD8alpha(+) DC that mediate cross-presentation of Ag to CD8 T cells specific for cell-associate Ags.
Gao
Jian-Xin
JX
Division of Cancer Immunology, Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.
Liu
Xingluo
X
Wen
Jing
J
Zhang
Huiming
H
Durbin
Joan
J
Liu
Yang
Y
Zheng
Pan
P
D016475:3T3 Cells; D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007114:Immunization; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D009368:Neoplasm Transplantation; D050794:STAT1 Transcription Factor; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
D016827:CD8 Antigens; C431698:CD8alpha antigen; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53