Treatment of neonatal mice with Flt3 ligand leads to changes in dendritic cell subpopulations associated with enhanced IL‐12 and IFN‐α production

• Published in: European Journal of Immunology Vol. 34; no. 7; pp. 1849 - 1860
• Main Authors: Vollstedt, Sabine, O'Keeffe, Meredith, Odermatt, Bernhard, Beat, Ryf, Glanzmann, Bettina, Riesen, Matthias, Shortman, Ken, Suter, Mark
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.07.2004
• Subjects: Animals; Animals, Newborn; Cell Differentiation - drug effects; Cell Lineage - drug effects; Cytokine production; DC subpopulations; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Flow Cytometry; Flt3 ligand; Interferon-alpha - biosynthesis; Interleukin-12 - biosynthesis; Lymphocyte Activation - drug effects; Lymphocyte Culture Test, Mixed; Male; Membrane Proteins - pharmacology; Mice; Mice, Inbred C57BL; Neonatal mice; Phenotype; T-Lymphocytes - immunology
• ISSN: 0014-2980; 1521-4141; 1365-2567
• DOI: 10.1002/eji.200324443

Treatment with the hematopoietic growth factor Flt3 ligand (FL) increases DC numbers in neonatal mice and enhances their resistance against intracellular pathogens. Flow cytometric analysis showed the presence of conventional DC (cDC) and plasmacytoid pre‐DC (pDC) in neonatal spleens from untreated and FL‐treated mice. CD8α and MHC class II expression on cDC and pDC was higher on DC from FL‐treated mice than on DC from control littermates. After FL treatment, two additional subpopulations of DC‐lineage cells were found that were able to produce IL‐12 and IFN‐α. The IL‐12 production of cDC from FL‐treated animals was more than 50‐fold increased and their ability to stimulate T cell proliferation was also increased. We conclude that the enhanced resistance against intracellular pathogens was due to increased numbers of DC‐lineage cells and their increased ability to produce the essential cytokines.