title: Immune tolerance induced by intravenous transfer of immature dendritic cells via up-regulating numbers of suppressive IL-10(+) IFN-γ(+)-producing CD4(+) T cells.
abstract: Dendritic cells (DCs) regulate immunity and immune tolerance in vivo. However, the mechanisms of DC-mediated tolerance have not been fully elucidated. Here, we demonstrate that intravenous (i.v.) transfer of bone marrow-derived DCs pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide blocks the development of experimental autoimmune encephalomyelitis in C57BL/6J mice. i.v. transfer of MOG-pulsed DCs leads to the down-regulation of the production of IL-17A and IFN-γ and up-regulation of IL-10 secretion. The development of regulatory T cells (Tregs) is facilitated via up-regulation of FoxP3 expression and production of IL-10. The number of suppressive CD4(+)IL-10(+)IFN-γ(+) T cells is also improved. The expression of OX40, CD154, and CD28 is down-regulated, but the expression of CD152, CD80, PD-1, ICOS, and BTLA is up-regulated on CD4(+) T cells after i.v. transfer of immature DCs. The expression of CCR4, CCR5, and CCR7 on CD4(+) T cells is also improved. Our results suggest that immature DCs may induce tolerance via facilitating the development of CD4(+)FoxP3(+) Tregs and suppressive CD4(+)IL-10(+)IFN-γ(+) T cells in vivo.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D019707:Receptors, Chemokine; D016753:Interleukin-10; D007371:Interferon-gamma