Mature bone marrow-derived dendritic cells polarize Th2 response and suppress experimental autoimmune encephalomyelitis.
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-gamma 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-gamma, 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.
Zhang
G X
GX
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Kishi
M
M
Xu
H
H
Rostami
A
A
D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000737:chemistry / Q000166:cytology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor