LPS and Freund's adjuvant initiate different inflammatory circuits in experimental autoimmune thyroiditis.
Although adjuvants are essential for the initiation of experimental autoimmune diseases, their precise contribution to the pathological manifestations is still poorly understood. Experimental autoimmune thyroiditis (EAT) is interesting in that respect because it can be initiated with the help of two different adjuvants   Freund's complete or LPS   which may initiate independent pathogenic pathways. In the present study, we have compared Freund's-induced versus LPS-induced EAT with respect to their dependence upon CD8+ T cells, which are considered as major actors in the pathogenesis of thyroiditis. Our results reveal that whereas CD8+ T cells are mandatory in the Freund's model, they can be bypassed in the LPS model. On the basis of this finding, we have examined the possibility that LPS may act directly upon in vitro cultured thyrocytes with no intermediate cell stages. Indeed, LPS triggers transcription and protein synthesis of several chemokines such as MIP-3alpha, RANTES, MCP-1 or TARC. Thus, beside enhancing the immunogenicity of autoantigens, probably via antigen trafficking and presentation, adjuvants such as LPS directly interact with the target organ through synthesis and release of powerful T cell attractants that facilitate its lymphocytic infiltration.
Damotte
Diane
D
Hôpital Européen Georges Pompidou, Service d'Anatomie et Cytologie Pathologiques, 20-40, rue Leblanc, 75015 Paris, France. diane.damotte@hop.egp.ap-hop-paris.fr
Goulvestre
Claire
C
Charreire
Jeannine
J
Carnaud
Claude
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D017931:DNA Primers; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D017931:DNA Primers; D008070:Lipopolysaccharides; D001613:beta 2-Microglobulin