Submitted July 17, 2006
Accepted December 20, 2006
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
Matthias Bros, Frank Jahrling, Andrea Renzing, Nadine Wiechmann, Ngoc-Anh Dang, Arne Sutter, Ralf Ross, Jurgen Knop, Stephan Sudowe, and Angelika B. Reske-Kunz*
Clinical Research Unit Allergology, Dept of Dermatology, Johannes Gutenberg-University, Mainz, Germany
Global Preclinical R&D Oncology Research Darmstadt, Merck KGaA, Darmstadt, Germany
* Corresponding author; email: a.reske-kunz{at}uni-mainz.de.
The phenotype and function of murine dendritic cells (DCs) are primarily studied using bone-marrow-derived dendritic cells (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 GM-CSF and M-CSF, SP37A3 cells resemble immature DCs characterized by low expression of 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 as compared with mature cells, as well as upregulated expression of Fc
RIIB and 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, mature as well as tolerogenic myeloid dendritic cells, circumventing restrictions associated with the use of primary DCs and BM-DCs.
