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Disease‐modifying capability of murine Flt3‐ligand DCs in experimental autoimmune encephalomyelitis
Author(s) -
Papenfuss Tracey L.,
Kithcart Aaron P.,
Powell Nicole D.,
McClain Melanie A.,
Gienapp Ingrid E.,
Shawler Todd M.,
Whitacre Caroline C.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0406257
Subject(s) - cd80 , experimental autoimmune encephalomyelitis , immunology , cd86 , biology , immune system , priming (agriculture) , dendritic cell , autoimmune disease , encephalomyelitis , t cell , in vitro , cd40 , cytotoxic t cell , antibody , multiple sclerosis , biochemistry , botany , germination
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‐α. Mature mFL BM‐DCs were immunogenic and exacerbated the clinical disease course of EAE.