The effects of anti-histone H1 antibody on immune cells responsible for rejection reaction.
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.
Hsu
Li-Wen
LW
Department of Surgery, Liver Transplant Center, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Rd., Niao-Sung Hsiang, Kaohsiung Hsien 833, Taiwan.
Goto
Shigeru
S
Nakano
Toshiaki
T
Lai
Chia-Yun
CY
Kao
Ying-Hsien
YH
Lin
Yu-Chun
YC
Kawamoto
Seiji
S
Ono
Kazuhisa
K
Lord
Roger
R
Goto
Takeshi
T
Omori
Naoya
N
Sato
Shuji
S
Chiang
Kuei-Chen
KC
Chen
Shu-Hui
SH
Jawan
Bruno
B
Cheng
Yu-Fan
YF
Chiu
King-Wah
KW
Chen
Chao-Long
CL
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*
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