title: Identification of CD8alpha+CD11c- lineage phenotype-negative cells in the spleen as committed precursor of CD8alpha+ dendritic cells.
abstract: CD8alpha+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8alpha+ DCs remains to be identified. We reported here that murine splenic CD8alpha+CD11c- lineage phenotype (Lin)- cells could differentiate into CD8alpha+ DCs in vivo after intravenous transplantation. Immunohistochemistry staining showed that donor-derived DCs mainly located in T-cell areas of the spleen. Functionally, these CD8alpha+CD11c-Lin- cell-derived DCs were capable of stimulating allogenic T-cell response, as well as secreting bioactive interleukin 12 p70 and interferon gamma. Freshly isolated CD8alpha+CD11c-Lin- cells expressed CC chemokine receptor (CCR)2, CCR5, and CCR7 messenger RNA, whereas CD8alpha+ DCs derived from CD8alpha+CD11c-Lin- cells further obtained the expression of CCR6 and macrophage-derived chemokine. Flow cytometry analysis showed that CD8alpha+CD11c-Lin- cells were identified in bone marrow and lymph nodes. Moreover, transplanted splenic CD8alpha+CD11c-Lin- cells could also home to thymus and lymph nodes and were capable of developing into CD8alpha+ DCs in these locations. However, CD8alpha+CD11c-Li- cells failed to differentiate into CD8alpha- DCs, T cells, natural killer cells, or other myeloid lineage cells in irradiated chimeras. Taken together, all these findings suggest that CD8alpha+CD11c-Lin- cells are a committed precursor of CD8alpha+ DCs.
authors.affiliation: Department of Molecular Preventive Medicine and CREST, School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Onai
authors.forename: Taku
authors.initials: T
authors.lastname: Sato
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology*; D002465:Cell Movement; D017690:Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D016130:Immunophenotyping; D016167:Integrin alphaXbeta2 / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology*
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D016207:Cytokines; D016167:Integrin alphaXbeta2; D019707:Receptors, Chemokine