Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulin-specific CD4+CD25+ T cells.

• Abstract: 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.
• Authors: Panayotis Verginis, Haiyan S Li, George Carayanniotis (Affiliation: Divisions of Endocrinology and Basic Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.)
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 11 Pg. 7433-9 (Jun 1 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15905592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Epitopes, T-Lymphocyte
• Receptors, Interleukin-2
• Interleukin-10
• Thyroglobulin

Topics

• Adoptive Transfer (methods)
• Animals
• Bone Marrow Cells (cytology)
• Cell Communication (immunology)
• Cell Differentiation (immunology)
• Cells, Cultured
• Cytokines (antagonists & inhibitors, biosynthesis)
• Dendritic Cells (cytology, immunology, transplantation)
• Epitopes, T-Lymphocyte (immunology, pharmacology)
• Female
• Immune Tolerance
• Immunophenotyping
• Interleukin-10 (secretion)
• Lymphocyte Activation (immunology)
• Mice
• Mice, Inbred CBA
• Mice, Inbred ICR
• Receptors, Interleukin-2 (biosynthesis)
• T-Lymphocytes, Regulatory (cytology, immunology, metabolism, secretion)
• Thyroglobulin (immunology, pharmacology)
• Thyroiditis, Autoimmune (immunology, prevention & control)