Tolerance to autoimmune thyroiditis: (CD4+)CD25+ regulatory T cells influence susceptibility but do not supersede MHC class II restriction.
Murine experimental autoimmune thyroiditis (EAT), a model of Hashimoto's thyroiditis, has served for more than three decades as a prototypical model of T cell-mediated autoimmunity. Early investigations demonstrated a clear correlation between genetic factors, particularly the H2A locus of the MHC class II region, and susceptibility to autoimmune thyroiditis. Early studies also demonstrated that susceptibility to EAT induction could be modulated by manipulation of circulating levels of thyroglobulin (Tg), the principal thyroid antigen, resulting in the strengthening of self-tolerance. This antigen-specific induced tolerance is mediated by thymus-derived cells, and subsequent investigations revealed that the suppressive function is located in the (CD4+)CD25+ T cell subset, similar to findings in other models. We have demonstrated that these (CD4+)CD25+ regulatory T cells (Treg) influence susceptibility to thyroiditis in naive, as well as mTg-tolerized mice. Here, we describe the influence of both Treg and MHC class II haplotype, independently, as well in combination, and describe our recent utilization of MHC class II transgenic mice to directly compare the extent of their influences.
Morris
Gerald P
GP
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Kong
Yi-chi M
YC
D000818:Animals; D000941:Antigens / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008954:Models, Biological; D008957:Models, Genetic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000473:pathology*
D000941:Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2