A single intratracheal dose of the growth factor Fms-like tyrosine kinase receptor-3 ligand induces a rapid differential increase of dendritic cells and lymphocyte subsets in lung tissue and bronchoalveolar lavage, resulting in an increased local antibody production.
Repetitive doses of the growth factor Fms-like tyrosine kinase receptor-3 ligand (Flt3L) have resulted in increased numbers of dendritic cells (DC) in various organs, and the effect on protective or tolerogeneic responses in the gut wall has been documented in the literature. In this study, for the first time, Flt3L was locally applied in the trachea of rats using a single dose only. A dose-dependent increase not only of DC, but also of T lymphocytes (CD4(+) and CD8(+)), was seen with a maximum on day 3. The effects on the cells in the lung interstitium and the bronchoalveolar space showed some differences. The use of tetanus toxoid as a model Ag applied intratracheally after the local Flt3L stimulation resulted in increased levels of specific IgA and IgG in the lung. Thus, this novel approach of locally stimulating APCs by topical application of a DC growth factor before applying the Ag offers a new vaccination strategy.
Pabst
Reinhard
R
Department of Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany. pabst.reinhard@mh-hannover.de
Lührmann
Anke
A
Steinmetz
Ivo
I
Tschernig
Thomas
T
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology; D000581:Amidohydrolases; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D008024:Ligands; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008024:Ligands; D008565:Membrane Proteins; D013745:Tetanus Toxoid; C084881:flt3 ligand protein; D040281:Vascular Endothelial Growth Factor Receptor-1; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase