Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulin-specific CD4+CD25+ T cells.
Ex vivo treatment of bone marrow-derived dendritic cells (DCs) with TNF-alpha has been previously shown to induce partial maturation of DCs that are able to suppress autoimmunity. In this study, we demonstrate that i.v. administration of TNF-alpha-treated, semimature DCs pulsed with thyrogloblin (Tg), but not with OVA Ag, inhibits the subsequent development of Tg-induced experimental autoimmune thyroiditis (EAT) in CBA/J mice. This protocol activates CD4(+)CD25(+) T cells in vivo, which secrete IL-10 upon specific recognition of Tg in vitro and express regulatory T cell (Treg)-associated markers such as glucocorticoid-induced TNFR, CTLA-4, and Foxp3. These CD4(+)CD25(+) Treg cells suppressed the proliferation and cytokine release of Tg-specific, CD4(+)CD25(-) effector cells in vitro, in an IL-10-independent, cell contact-dependent manner. Prior adoptive transfer of the same CD4(+)CD25(+) Treg cells into CBA/J hosts suppressed Tg-induced EAT. These results demonstrate that the tolerogenic potential of Tg-pulsed, semimature DCs in EAT is likely to be mediated through the selective activation of Tg-specific CD4(+)CD25(+) Treg cells and provide new insights for the study of Ag-specific immunoregulation of autoimmune diseases.
Verginis
Panayotis
P
Divisions of Endocrinology and Basic Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Li
Haiyan S
HS
Carayanniotis
George
G
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013954:Thyroglobulin / Q000276:immunology* / Q000494:pharmacology; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000517:prevention & control*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D013954:Thyroglobulin