Conditional expression of murine Flt3 ligand leads to expansion of multiple dendritic cell subsets in peripheral blood and tissues of transgenic mice.
The analysis of the development and function of distinct subsets of murine dendritic cells (DC) has been hampered by the limited number of these cells in vivo. To circumvent this limitation we have developed a conditional transgenic mouse model for producing large numbers of DC. We used the tetracycline-inducible system to conditionally express murine Flt3 ligand (FL), a potent hemopoietic growth factor that promotes the differentiation and mobilization of DC. Acute treatment (96 h) of the transgenic animals with the tetracycline analog doxycycline (DOX) promoted an approximately 200-fold increase in serum levels of FL without affecting the number of circulating DC. However, within 1 wk of DOX treatment, the relative number of DC in peripheral blood increased from approximately 8 to approximately 40%. Interestingly, both the levels of FL and the number of DC remained elevated for at least 9 mo with continual DOX treatment. Chronic treatment of the mice with DOX led to dramatic increases in the number of DC in multiple tissues without any apparent pathological consequences. Most DC populations were expanded, including immature and mature DC, myeloid (CD11c(+)CD11b(+)CD8a(-)), lymphoid (CD11c(+)CD11b(-)CD8a(+)), and the recently defined plasmacytoid (pDC) subsets. Finally, transplantation of BM from green fluorescent protein-expressing mice into lethally irradiated transgenic mice followed by subsequent DOX treatment led to expansion of green fluorescent protein-labeled DC. The transgenic mice described here should thus provide a readily available source of multiple DC subsets and should facilitate the analysis of their role in homeostasis and disease.
Manfra
Denise J
DJ
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Chen
Shu-Cheng
SC
Jensen
Kristian K
KK
Fine
Jay S
JS
Wiekowski
Maria T
MT
Lira
Sergio A
SA
D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis / Q000097:blood; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D049452:Green Fluorescent Proteins; D016130:Immunophenotyping; D008024:Ligands; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D039521:CD11c Antigen; D008024:Ligands; D008164:Luminescent Proteins; D008565:Membrane Proteins; C084881:flt3 ligand protein; D049452:Green Fluorescent Proteins; D004318:Doxycycline