title: Unexpected T cell regulatory activity of anti-histone H1 autoantibody: its mode of action in regulatory T cell-dependent and -independent manners.
abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4(+-)Foxp3(+) Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.
authors: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors: Yuki
authors: Y
authors: Takaoka
authors: Seiji
authors: S
authors: Kawamoto
authors: Akiko
authors: A
authors: Katayama
authors: Toshiaki
authors: T
authors: Nakano
authors: Yasushi
authors: Y
authors: Yamanaka
authors: Miki
authors: M
authors: Takahashi
authors: Yayoi
authors: Y
authors: Shimada
authors: Kuei-Chen
authors: KC
authors: Chiang
authors: Naoya
authors: N
authors: Ohmori
authors: Tsunehiro
authors: T
authors: Aki
authors: Takeshi
authors: T
authors: Goto
authors: Shuji
authors: S
authors: Sato
authors: Shigeru
authors: S
authors: Goto
authors: Chao-Long
authors: CL
authors: Chen
authors: Kazuhisa
authors: K
authors: Ono
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006657:Histones / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D006657:Histones; D011948:Receptors, Antigen, T-Cell