Journal Article

The role of dendritic cells in the generation of CD4<sup>+</sup> CD25<sup>HI</sup> Foxp3<sup>+</sup> T cells induced by amino acid copolymers

Norio Kawamoto, Hidenori Ohnishi, Naomi Kondo and Jack L. Strominger

in International Immunology

Volume 25, issue 1, pages 53-65
Published in print January 2013 | ISSN: 0953-8178
Published online September 2012 | e-ISSN: 1460-2377 | DOI: http://dx.doi.org/10.1093/intimm/dxs087
The role of dendritic cells in the generation of  CD4+ CD25HI Foxp3+ T cells induced by amino  acid copolymers

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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+ CD25HI Foxp3 T cells (~25% of which were Foxp3+). The number of these regulatory cells was doubled by pretreatment of BMDC with amino acid copolymers.

Keywords: BMDC; CCL22; Copaxone; EAE; macrophages; MHC II−/−; mice; regulatory T cells

Journal Article.  7023 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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