Flt3 ligand preferentially increases the number of functionally active myeloid dendritic cells in the lungs of mice.
In the present study, we investigated the effects of in vivo Flt3L administration on the generation, phenotype, and function of lung dendritic cells (DCs) to evaluate whether Flt3L favors the expansion and maturation of a particular DC subset. Injection of Flt3L into mice resulted in an increased number of CD11c-expressing lung DCs, preferentially in the alveolar septa. FACS analysis allowed us to quantify a 19-fold increase in the absolute numbers of CD11c-positive, CD45R/B220 negative DCs in the lungs of Flt3L-treated mice over vehicle-treated mice. Further analysis revealed a 90-fold increase in the absolute number of myeloid DCs (CD11c positive, CD45R/B220 negative, and CD11b positive) and only a 3-fold increase of lymphoid DCs (CD11c positive, CD45R/B220 negative, and CD11b negative) from the lungs of Flt3L-treated mice over vehicle-treated mice. Flt3L-treated lung DCs were more mature than vehicle-treated lung DCs as demonstrated by a significantly higher percentage of cells expressing MHC class II, CD86, and CD40. Freshly isolated Flt3L lung DCs were not fully mature, because after an overnight culture they continued to increase accessory molecule expression. Functionally, Flt3L-treated lung DCs were more efficient than vehicle-treated DCs at stimulating naive T cell proliferation. Our data show that administration of Flt3L favors the expansion of myeloid lung DCs over lymphoid DCs and enhanced their ability to stimulate naive lymphocytes.
Masten
Barbara J
BJ
Department of Pathology, University of New Mexico, Albuquerque, NM 87131, USA. bmasten@salud.unm.edu
Olson
Gwyneth K
GK
Kusewitt
Donna F
DF
Lipscomb
Mary F
MF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000096:biosynthesis; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007399:Interphase / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007958:Leukocyte Count; D008024:Ligands; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008565:Membrane Proteins; C084881:flt3 ligand protein; D017493:Leukocyte Common Antigens