Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Leukoc Biol. 2007 Dec;82(6):1510-8. Epub 2007 Sep 12.

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

Author information

  • 1Departments of Veterinary Biosciences, The Ohio State University, 370 Veterinary Medical Academic Building, 1900 Coffey Road, Columbus, OH 43210, USA. papenfuss.1@osu.edu

Abstract

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.

PMID:
17855499
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk