A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid

• Published in: Blood 2007-05, Vol.109 (9), p.3820-3829
• Main Authors: Bros, Matthias, Jährling, Frank, Renzing, Andrea, Wiechmann, Nadine, Dang, Ngoc-Anh, Sutter, Arne, Ross, Ralf, Knop, Jürgen, Sudowe, Stephan, Reske-Kunz, Angelika B.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Line; Cell Proliferation - drug effects; Clonal Anergy - drug effects; Clonal Anergy - immunology; Coculture Techniques; Cytokines - immunology; Dendritic Cells - cytology; Dendritic Cells - immunology; Dexamethasone - pharmacology; Glucocorticoids - pharmacology; Histocompatibility Antigens Class II - immunology; Interleukin 1 Receptor Antagonist Protein - immunology; Mice; Mice, Inbred BALB C; Myeloid Progenitor Cells - cytology; Myeloid Progenitor Cells - immunology; Receptors, IgG - immunology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Up-Regulation - drug effects; Up-Regulation - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-07-035576

The phenotype and function of murine dendritic cells (DCs) are primarily studied using bone-marrow–derived DCs (BM-DCs), but may be hampered by the heterogenous phenotype of BM-DCs due to their differential state of maturation. Here we characterize a newly established murine DC line (SP37A3) of myeloid origin. During maintainance in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and M-CSF, SP37A3 cells resemble immature DCs characterized by low expression of major histocompatibility complex (MHC) II and costimulatory molecules and low T-cell stimulatory capacity. Upon stimulation, SP37A3 cells acquire a mature phenotype and activate naive T cells as potently as BM-DCs. Similar to BM-DCs, SP37A3 cells activated in the presence of dexamethasone-induced regulatory T cells, which were anergic upon restimulation and suppressed proliferation of naive T cells. This tolerogenic state was reflected by lower expression levels of costimulatory molecules and proinflammatory cytokines compared with mature cells, as well as up-regulated expression of FcγRIIB and interleukin-1RA (IL-1RA). SP37A3 cells were responsive to dexamethasone even when applied at later time points during activation, suggesting functional plasticity. Thus, DC line SP37A3 represents a suitable model to study functions of immature and mature as well as tolerogenic myeloid DCs, circumventing restrictions associated with the use of primary DCs and BM-DCs.