Differentiation of myeloid dendritic cells into CD8alpha-positive dendritic cells in vivo.
Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8alpha(+) and CD8alpha(-) DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8alpha, but they do express high levels of myeloid antigens such as CD11b and FcgammaR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8alpha but only low levels of myeloid antigens. CD8alpha(+) DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8alpha(-) epidermal LC in vivo, it was found that these cells expressed CD8alpha on migration to the draining LN. Similarly, CD8alpha(-) LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8alphaKO mouse expressed CD8alpha when they reached the draining LN. The results also show that CD8alpha(+) LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-gamma, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8alpha when they migrate to the draining LN. CD8alpha expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage. (Blood. 2000;96:1865-1872)
Merad
M
M
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. meradm@leland.stanford.edu
Fong
L
L
Bogenberger
J
J
Engleman
E G
EG
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
C106311:CCR6 protein, human; C515370:CCR7 protein, human; D017252:CD3 Complex; D016827:CD8 Antigens; C515371:Ccr7 protein, mouse; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019707:Receptors, Chemokine