Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified.
Dendritic cells (DC) are the most efficient APC for T cells. The clinical use of DC as vectors for anti-tumor and infectious disease immunotherapy has been limited by their trace levels and accessibility in normal tissue and terminal state of differentiation. In the present study, daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. In contrast, in mice treated with either GM-CSF, GM-CSF plus IL-4, c-kit ligand (c-kitL), or G-CSF, class II+ CD11c+ cells were not significantly increased. Five distinct DC subpopulations were identified in the spleen of Flt3L-treated mice using CD8 alpha and CD11b expression. These cells exhibited veiled and dendritic processes and were as efficient as rare, mature DC isolated from the spleens of untreated mice at presenting allo-Ag or soluble Ag to T cells, or in priming an Ag-specific T cell response in vivo. Dramatic numerical increases in DC were detected in the bone marrow, gastro-intestinal lymphoid tissue (GALT), liver, lymph nodes, lung, peripheral blood, peritoneal cavity, spleen, and thymus. These results suggest that Flt3L could be used to expand the numbers of functionally mature DC in vivo for use in clinical immunotherapy.
Maraskovsky
E
E
Department of Immunobiology, Immunex Corporation, Seattle, Washington 98101, USA.
Brasel
K
K
Teepe
M
M
Roux
E R
ER
Lyman
S D
SD
Shortman
K
K
McKenna
H J
HJ
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD; D016827:CD8 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2 / Q000032:analysis; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019089:Stem Cell Factor / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution
D015703:Antigens, CD; D016827:CD8 Antigens; C093569:DEC-205 receptor; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor