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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3820-3829. Prepublished online as a Blood First Edition Paper on January 5, 2007; DOI 10.1182/blood-2006-07-035576.
IMMUNOBIOLOGY 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 glucocorticoid1 Clinical Research Unit Allergology, Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany; 2 Global Preclinical R&D Oncology Research Darmstadt, Merck, Darmstadt, Germany
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 Fc
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||||
RIIB 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. 