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.