The role of dendritic cells in the generation of CD4+ CD25HI 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-erived 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. © The Japanese Society for Immunology. 2012. All rights reserved.