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Mature bone marrow-derived dendritic cells polarize Th2 response and suppress experimental autoimmune encephalomyelitis

Department of Neurology, University of Pennsylvania School of Medicine, 3400 and Spruce St., Philadelphia, Pennsylvania 19104, USA

M Kishi

Department of Neurology, University of Pennsylvania School of Medicine, 3400 and Spruce St., Philadelphia, Pennsylvania 19104, USA

H Xu

Department of Neurology, University of Pennsylvania School of Medicine, 3400 and Spruce St., Philadelphia, Pennsylvania 19104, USA

A Rostami

Department of Neurology, University of Pennsylvania School of Medicine, 3400 and Spruce St., Philadelphia, Pennsylvania 19104, USA, rostamia{at}mail.med.upenn.edu

Distinct subsets of dendritic cells (DCs) based on the origin, phenotypes, and the nature of the signals that promote DC maturation can determine polarized immune responses of T cells. In this study, DCs were cultured from mouse bone marrow (BM) progenitors in granulocyte-macrophage colony-stimulating factor (GM-CSF). To generate mature DCs (mDCs), lipopolysaccharide (LPS) was used in the culture for 24 h. LPS-stimulated DCs were phenotypically mature, which exhibited strongly upregulated CD40, B7.1, and B7.2 compared to non-LPS-stimulated immature DCs (imDCs). Both mDCs and imDCs expressed high levels of MHC class II but low level of CD54. mDCs produced higher levels of IL-10 and lower IL-12 compared to imDCs. No IFN-g or IL-4 was found in both groups. When mDCs were injected intraperitoneally (i.p.) to the mice with experimental autoimmune encephalomyelitis (EAE), the severity of clinical signs and inflammation in the CNS was significantly suppressed compared to imDC-injected mice (p<0.01) and PBS-injected mice (p <0.02). Moreover, lymphocytes from mDC-injected mice produced lower level of IL-12, IFN-g, but higher level of IL-10, compared to imDC-injected and non-DC-injected mice. We conclude that BM-mDCs, but not BM-imDCs, promote Th2 differentiation and have the potential for suppression of inflammatory demyelination.

Key Words: cytokines • dendritic cells • experimental autoimmune encephalomyelitis • multiple sclerosis • Th1/Th2

Multiple Sclerosis, Vol. 8, No. 6, 463-468 (2002)
DOI: 10.1191/1352458502ms857oa


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