Identification of CD8alpha+CD11c- lineage phenotype-negative cells in the spleen as committed precursor of CD8alpha+ dendritic cells

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 p...

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Bibliographic Details
Published in:Blood 2002-07, Vol.100 (2), p.569-577
Main Authors: Wang, Yong, Zhang, Yanyun, Yoneyama, Hiroyuki, Onai, Nobuyuki, Sato, Taku, Matsushima, Kouji
Format: Article
Language:English
Subjects:
Animals
CD8 Antigens - analysis
Cell Differentiation
Cell Lineage - immunology
Cell Movement
Cell Transplantation
Cytokines - metabolism
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Hematopoietic Stem Cells - cytology
Immunophenotyping
Integrin alphaXbeta2 - analysis
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred BALB C
Receptors, Chemokine - metabolism
Spleen - cytology
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Summary: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.
ISSN:0006-4971