An Ox-2:fc Immunoadhesin Is a Potent Immunosuppressant Facilitating Allo- And Xeno-Renal Graft Survival

Gorczynski, Reg; Chen, Z.; Hu, Jiang; Ji, Lei; Yu, Guolin; Ni, Jinfeng

doi:10.1097/00007890-199904150-00292

Cited by 80 publications

(146 citation statements)

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“…Thus CD200 is thought to provide a localized way of controlling myeloid activity in the tissues through its receptor. Consistent with this are data showing that cell-cell contact leads to down-regulation of myeloid cells through CD200R [5] and targeting the CD200R with Fc fusion proteins and antibodies can ameliorate autoimmune diseases [6,7]. CD200 and CD200R both contain two IgSF domains like many surface proteins at the leukocyte cell surface [2,8,9].…”

Section: Introductionsupporting

confidence: 58%

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

Hatherley

Barclay

2004

Eur J Immunol

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CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a receptor on myeloid cells (CD200R) involved in regulation of macrophage function. Both CD200 and CD200R contain two Ig superfamily domains like many other leukocyte membrane proteins. Site‐directed mutagenesis of CD200R showed that, like CD200, it interacted through its N‐terminal domain. This indicated that the cell‐cell interaction spans four Ig superfamily domains and this distance is similar to many interactions found between T cells and antigen‐presenting cells. This suggests that this topology is also important in interactions of CD200 on a variety of cells with CD200R on myeloid cells, and comparable contact sites may be important mediating regulation in other cell‐cell interactions. The mutagenesis showed that the binding involved the predicted GFCC′ face of its N‐terminal domain, like that of CD200, suggesting that the interaction evolved from a homotypic interaction.

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Section: Introductionsupporting

confidence: 58%

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

Hatherley

Barclay

2004

Eur J Immunol

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“…CD200-Fc, A NOVEL ANTIARTHRITIC BIOLOGIC AGENTCD200-Fc therapy was effective at a dosage of 1 mg/kg given every 2-3 days. This dosage was chosen because it was shown in previous studies to be consistently effective in preventing CIA as well as in transplantation experiments to be effective in promoting increased skin and renal graft survival (4,13). We also found that higher dosages of CD200-Fc did not prove to be more effective, and a lower dosage of 0.5 mg/kg showed evidence of efficacy, but the small numbers of mice treated precluded statistical analysis (data not shown).…”

Section: Discussionmentioning

confidence: 94%

CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis

Šimelyte

Criado

Essex

et al. 2008

Arthritis & Rheumatism

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Objective. The CD200 receptor (CD200R) is an inhibitory receptor expressed by myeloid cells that is postulated to play an important role in regulation of the immune system. The purpose of this study was to evaluate the efficacy of a soluble ligand of CD200R in established collagen-induced arthritis (CIA) in mice and to analyze changes in cytokine expression following therapy in order to understand its primary mechanism of action.Methods. Arthritis was induced in DBA/1 mice, and CD200-Fc fusion protein, an isotype control monoclonal antibody, or TNFR-Fc fusion protein was administered over a period of 10 days (total of 4 doses). Cytokine expression in the joint was assessed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction.Results. CD200-Fc significantly reduced the severity of established arthritis at the clinical and histologic levels. The therapeutic effect of CD200-Fc at 1 mg/kg was comparable with that of TNFR-Fc at 4 mg/kg. CD200R was found to be expressed in arthritic synovia and in lymph nodes, yet no changes in T cell cytokine levels (interferon-␥, interleukin-5 [IL-5], IL-10, IL-17) were detected after CD200-Fc therapy. There was no evidence of an expansion of forkhead box P3-positive regulatory T cells or a change in serum anticollagen IgG1 and IgG2a levels. However, administration of CD200-Fc markedly decreased the expression of messenger RNA for tumor necrosis factor ␣, IL-1␤, IL-10, and matrix metalloproteinase 13 in the joint to the same extent as administration of TNFR-Fc.Conclusion. CD200-Fc is an effective therapeutic agent in established CIA that targets proinflammatory cytokine expression in the joint without any obvious systemic immunosuppressive effects. Our findings indicate that CD200-Fc has considerable potential as a novel therapeutic agent in rheumatoid arthritis in humans.

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“…In addition, genetically engineering DC with the Th2/Th3 cytokines IL-10, TGF-␤, Fas ligand (24), CTLA-4, or Srrate (a ligand of Notch proteins) (40) results in Ag-specific tolerance (24,41) as well as the induction of Treg (42). Many previous studies have demonstrated the ability of tolerogenic DC to induce transplantation tolerance in various transplant models (24,(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Although some success in tolerance induction has been achieved in animal models using artificially manipulated tolerogenic DC, a clinically applicable method has not yet been developed.…”

Section: Discussionmentioning

confidence: 99%

Immune Modulation and Tolerance Induction by RelB-Silenced Dendritic Cells through RNA Interference

Zhang

Zheng

Lian

et al. 2007

The Journal of Immunology

118

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Dendritic cells (DC), the most potent APCs, can initiate the immune response or help induce immune tolerance, depending upon their level of maturation. DC maturation is associated with activation of the NF-κB pathway, and the primary NF-κB protein involved in DC maturation is RelB, which coordinates RelA/p50-mediated DC differentiation. In this study, we show that silencing RelB using small interfering RNA results in arrest of DC maturation with reduced expression of the MHC class II, CD80, and CD86. Functionally, RelB-silenced DC inhibited MLR, and inhibitory effects on alloreactive immune responses were in an Ag-specific fashion. RelB-silenced DC also displayed strong in vivo immune regulation. An inhibited Ag-specific response was seen after immunization with keyhole limpet hemocyanin-pulsed and RelB-silenced DC, due to the expansion of T regulatory cells. Administration of donor-derived RelB-silenced DC significantly prevented allograft rejection in murine heart transplantation. This study demonstrates for the first time that transplant tolerance can be induced by means of RNA interference using in vitro-generated tolerogenic DC.

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An Ox-2:fc Immunoadhesin Is a Potent Immunosuppressant Facilitating Allo- And Xeno-Renal Graft Survival

Cited by 80 publications

References 0 publications

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis

Immune Modulation and Tolerance Induction by RelB-Silenced Dendritic Cells through RNA Interference

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