title: The role of dendritic cells in the generation of CD4(+) CD25(HI) Foxp3(+) T cells induced by amino acid copolymers.
abstract: The effects of the amino acid copolymers used in the therapy of experimental autoimmune encephalomyelitis, poly(Y,E,A,K)(n) (Copaxone(®)) and poly(Y,F,A,K)(n), on murine myeloid cells have been investigated. After administration of these copolymers to mice, increases in several splenic myeloid cell populations were observed, including CD11b(+) CD11c(+) dendritic cells. The latter were the major splenic cell type that secreted CCL22 (macrophage-derived chemokine) on stimulation with amino acid copolymers. CCL22 secretion was also stimulated from bone marrow-derived dendritic cells (BMDC) generated with GM-CSF in much larger amounts than from bone marrow-derived macrophages generated with M-CSF. Moreover, CCL22 secretion could also be obtained using BMDC generated from two different types of MHC II(-/-) mice, indicating that an innate immune receptor is involved. Finally, incubation of these BMDC or splenic dendritic cells with naive CD4(+) CD25(-) T cells resulted in formation of CD4(+) CD25(HI) Foxp3 T cells (~25% of which were Foxp3(+)). The number of these regulatory cells was doubled by pretreatment of BMDC with amino acid copolymers.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue,  Cambridge, MA 02138, USA.
authors.forename: Norio
authors.initials: N
authors.lastname: Kawamoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D054422:Chemokine CCL22 / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D000068717:Glatiramer Acetate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008285:Major Histocompatibility Complex; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D009842:Oligopeptides; D010455:Peptides; D000068717:Glatiramer Acetate; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor