In contrast, the parent-into-F1 acute GVHD model, which is induced in BDF1 mice by the injection of

Related literature Cited by Google blog search Other articles by authors   on Google Scholar Kuroiwa T Iwasaki T Imado T Sekiguchi M Fujimoto J Sano H   on PubMed Kuroiwa T Iwasaki T Imado T Sekiguchi M Fujimoto J Sano H Related articles/pages on Google on Google Scholar on PubMed Tools Download references Download XML Email to a friend Order reprints Post a comment   Download to ... Papers Mendeley Download to ... Papers Mendeley Share this article
Author Affiliations
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/8/4/R123 Received: 17 April 2006 Revisions received: 6 July 2006 Accepted: 14 July 2006 Published: 19 July 2006
This is an open access article distributed under the terms of the Creative Commons wireless driveway alert Attribution License wireless driveway alert ( http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chronic graft-versus-host disease (GVHD) induced in (C57BL/6 DBA/2) F1 (BDF1) mice by the injection of DBA/2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC) and Sjogren's syndrome (SS), as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect wireless driveway alert of hepatocyte growth factor (HGF) gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 μg of the human HGF expression vector (HGF-HVJ liposomes) or mock vector (untreated control). Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated wireless driveway alert with glomerulonephritis. While liver and salivary gland sections wireless driveway alert from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced wireless driveway alert these histopathological changes. HGF gene transfection greatly reduced wireless driveway alert the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression wireless driveway alert on DBA/2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro . Furthermore, IL-4 production by DBA/2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro . These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune wireless driveway alert sialoadenitis, and cholangitis wireless driveway alert in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC. Introduction
Pathogenic T cells that recognize self-antigens and drive B cell hyperactivity play a central role in the pathogenesis of both human and murine lupus [ 1 - 3 ]. Chronic graft-versus-host disease wireless driveway alert (GVHD), which is induced in (C57BL/6 DBA/2) F1 (BDF1) mice by injection of DBA/2 spleen cells, is associated with the activation of donor CD4+ T cells that recognize host major histocompatibility complex (MHC) antigens and drive host B cell hyperactivity [ 4 , 5 ]. Mice of this parent-into-F1 chronic GVHD model show increased T helper (Th) 2 immune responses, wireless driveway alert and exhibit autoimmune disorders that resemble human systemic lupus erythematosus, primary biliary chirrhosis, and Sjogren's syndrome, which are characterized by lymphocyte infiltration into organs such as the kidneys, liver and salivary glands [ 6 ].
In contrast, the parent-into-F1 acute GVHD model, which is induced in BDF1 mice by the injection of C57BL/6 (B6) spleen cells, is associated with the activation of donor CD8+ cytotoxic T lymphocytes (CTLs) that recognize host MHC antigens and cause death by affecting host immune and hematopoietic systems [ 7 - 9 ]. As acute GVHD can be inhibited by the addition of neutralizing anti-IL-2 monoclonal antibodies (mAbs) and is not induced by perforin-deficient donor T cells [ 10 , 11 ], acute GVHD is associated wireless driveway alert with increased Th1-mediated immune responses and with perforin expression on donor T cells.
One wireless driveway alert of the principal distinctions between the acute and chronic GVHD models appears to be the nine-fold reduction in CTL precursor numbers with anti-host specificity (which eliminate autoreactive host B cells) generated during GVHD induced by DBA/2 mouse spleen cells rather than by B6 mouse spleen cells [ 12 ]. Previous experiments have demonstrated that cytokines such as IL-12 and IL-18 induce donor anti-host CTLs in chronic GVHD mice and can ameliorate chronic GVHD, or even stimulate the development of acute GVHD [ 13 , 14 ].
Recently, we demonstrated that repeated transfection of skeletal muscle with the gene encoding the h