Maturation of dendritic cells by necrotic thyrocytes facilitates induction of experimental autoimmune thyroiditis.
Dendritic cell (DC) maturation is required for efficient presentation of autoantigens leading to autoimmunity. In this report, we have examined whether release of tissue antigens from necrotic thyroid epithelial cells can trigger DC maturation and initiation of a primary anti-self response. DC were cocultured with either viable (VT/DC) or necrotic (NT/DC) thyrocytes, and their phenotypic and functional maturation as well as immunopathogenic potential were assessed. Significant up-regulation of surface MHC class II and costimulatory molecule expression was observed in NT/DC but not in VT/DC. This was correlated with a functional maturation of NT/DC, determined by IL-12 secretion. Challenge of CBA/J mice with NT/DC, but not with VT/DC, elicited thyroglobulin (Tg)-specific IgG as well as Tg-specific CD4(+) T-cell responses and led to development of experimental autoimmune thyroiditis. These results support the view that thyroid epithelial cell necrosis may cause autoimmune thyroiditis via maturation of intrathyroidal DC.
Li
H S
HS
Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Verginis
P
P
Carayanniotis
G
G
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009336:Necrosis / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
D001324:Autoantigens; D007074:Immunoglobulin G; D018664:Interleukin-12; D013954:Thyroglobulin