The role of dendritic cells in the generation of CD4 CD25HI Foxp3 T cells induced by amino acid copolymers

Therapeutic amino-acid copolymers stimulate innate myeloid-cell responses in EAE.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 (similar to 25% of which were Foxp3). The number of these regulatory cells was doubled by pretreatment of BMDC with amino acid copolymers.