Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0406257 on September 12, 2007

Published online before print September 12, 2007
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(Journal of Leukocyte Biology. 2007;82:1510-1518.)
© 2007 by Society for Leukocyte Biology

Disease-modifying capability of murine Flt3-ligand DCs in experimental autoimmune encephalomyelitis

Tracey L. Papenfuss*,1, Aaron P. Kithcart{dagger}, Nicole D. Powell{ddagger}, Melanie A. McClain{dagger}, Ingrid E. Gienapp{dagger}, Todd M. Shawler{dagger} and Caroline C. Whitacre{dagger}

* Departments of Veterinary Biosciences and
{dagger} Molecular Virology, Immunology and Medical Genetics, and
{ddagger} Section of Oral Biology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA

1Correspondence: Department of Veterinary Biosciences, The Ohio State University, 370 Veterinary Medical Academic Building, 1900 Coffey Road, Columbus, OH 43210, USA. E-mail: papenfuss.1{at}osu.edu

Dendritic cells (DCs) bridge the innate and adaptive immune response, are uniquely capable of priming naïve T cells, and play a critical role in the initiation and regulation of autoimmune and immune-mediated disease. At present, in vivo expansion of DC populations is accomplished primarily through the administration of the recombinant human growth factor fms-like tyrosine kinase 3 ligand (hFL), and in vitro DCs are generated using cytokine cocktails containing GM-CSF ± IL-4. Although hFL has traditionally been used in mice, differences in amino acid sequence and biological activity exist between murine FL (mFL) and hFL, and resultant DC populations differ in phenotype and immunoregulatory functional capabilities. This study developed and characterized mFL-generated DCs and determined the therapeutic capability of mFL DCs in the autoimmune disease experimental autoimmune encephalomyelitis (EAE). Our findings demonstrate that mFL and hFL expand splenic DCs equally in vivo but that mFL-expanded, splenic DCs more closely resemble normal, resting, splenic DCs. In addition, a novel method for generating mFL-derived bone marrow-derived DCs (BM-DCs) was developed, and comparison of mFL with hFL BM-DCs found mFL BM-DCs to be less mature (i.e., lower MHC Class II, CD80, and CD86) than hFL BM-DCs. These immature mFL DCs up-regulated costimulatory molecules in response to maturation stimuli LPS and TNF-{alpha}. Mature mFL BM-DCs were immunogenic and exacerbated the clinical disease course of EAE.

Key Words: dendritic cells • MS/EAE







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