title: The effects of anti-histone H1 antibody on immune cells responsible for rejection reaction.
abstract: We previously demonstrated the immunosuppressive activity of anti-histone H1 autoreactive antibodies (Ab) transiently induced in serum of a rat tolerogenic orthotopic liver transplantation (OLT) model. In the present study, we investigated the effects of anti-histone H1 Ab on dendritic cells (DCs), T-cells, lymphokine-activated killer (LAK) cells, and human natural killer (NK) cells. The effects of anti-histone H1 Ab on Concanavalin A (ConA) blast, on rat DC cytokine profiles and phenotypes, and on T-cells, LAK cells, and human NK cells were examined by flow cytometry and RT-PCR. The cytotoxicity of LAK and NK cells pretreated with anti-histone H1 Ab was assayed. The addition of anti-histone H1 Ab to ConA blast inhibited the proliferation of 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE)-labeled lymphocytes without toxicity but increased the population of CD4+CD25+ T-cells. DCs treated with anti-histone H1 Ab expressed lower levels of CD80/CD86, IL-1beta, and IL-6. The addition of anti-histone H1 Ab to LAK culture decreased the percentages of NKR-P1 populations and down-regulated levels of inducible nitric oxide synthase (iNOS), IL-2, and INF-gamma in RT-PCR. The cytotoxicity of LAK and NK cells was lower when pretreated with anti-histone H1 Ab than when pretreated with control IgG. We found that the blockade of histone H1 modulated DCs toward tolerogenic status, decreased the cytotoxicity of LAK and NK cells, and induced CD4+CD25+ T-cells. These results suggest that the use of anti-histone H1 Abs might be a useful strategy for the development of a form of immunosuppression.
authors.affiliation: Department of Surgery, Liver Transplant Center, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Rd., Niao-Sung Hsiang, Kaohsiung Hsien 833, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ono
authors.forename: Roger
authors.initials: R
authors.lastname: Lord
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.forename: Naoya
authors.initials: N
authors.lastname: Omori
authors.forename: Shuji
authors.initials: S
authors.lastname: Sato
authors.forename: Kuei-Chen
authors.initials: KC
authors.lastname: Chiang
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: Bruno
authors.initials: B
authors.lastname: Jawan
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.forename: King-Wah
authors.initials: KW
authors.lastname: Chiu
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D005434:Flow Cytometry; D006657:Histones / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D020014:K562 Cells; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006657:Histones; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat