title: Antigen-independent development of Foxp3+ regulatory T cells suppressing autoantibody production in experimental pemphigus vulgaris.
abstract: The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) play suppressive roles in various types of autoimmunity. It has been reported that Tregs develop in the thymus after high-affinity interaction of their TCR with self-peptide/MHC ligands mostly utilizing TCR-transgenic system. In this study, we examined whether the specific antigen is involved in the development of polyclonal Tregs in pemphigus vulgaris (PV), an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies, as a model system. Adoptive transfer of splenocytes of Dsg3(-)(/-) mice immunized with recombinant mouse Dsg3 to Rag2(-)(/-) recipient mice expressing Dsg3 resulted in the stable production of anti-Dsg3 IgG and the development of PV phenotypes. We show here that Tregs control anti-Dsg3 antibody production in PV model mice: the adoptive transfer of Tregs and the depletion of endogenous Tregs suppressed and augmented, respectively, the anti-Dsg3 antibody production. To examine whether the endogenous expression of Dsg3 is involved in the generation of these PV-relevant Tregs, we compared the potential of wild-type Tregs with that of Tregs from Dsg3(-)(/-) mice. Polyclonal Tregs from Dsg3(-)(/-) mice were more potent than that of wild-type mice, in both adoptive transfer and Treg-depletion experiments, while suppressive activities against IgG production against an irrelevant antigen were similar between Tregs from wild-type and Dsg3(-)(/-) mice. Our observation implies that Tregs capable of suppressing T(h) cells that drive autoantibody production can develop in the absence of the target antigen.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine,Tokyo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuda
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Takae
authors.forename: Naoko
authors.initials: N
authors.lastname: Wada
authors.forename: Takeji
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D051184:Desmoglein 3 / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010392:Pemphigus / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D001323:Autoantibodies; D051184:Desmoglein 3; C495300:Dsg3 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G