Specific Acceptance of Cardiac Allograft After Treatment with Antibodies to ICAM-1 and LFA-1

Isobe, Mitsuaki; Yagita, Hideo; Okumura, Ko; Ihara, Akira

doi:10.1126/science.1347662

Cited by 694 publications

(263 citation statements)

References 26 publications

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“…Additionally, CD54 can be expressed by almost all cell types, including glomerular endothelial cells (reviewed in [32]), which enables it to mediate the binding and migration of leucocytes to sites of inflammation in the tissues. Thus, in line with previous reports, interference with the CD11a/CD54 pathway may have affected lymphocyte interaction and autoantibody production [27,[33][34][35] and/or the glomerular inflammatory response [5,6,30]. Indeed, MoAb treatment in mice with GVHD decreased the presence of immunoglobulins and complement along the glomerular capillary walls.…”

Section: Discussionsupporting

confidence: 86%

Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies

Kootstra

Giezen

Krieken

et al. 1997

Clinical and Experimental Immunology

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SUMMARYMice with chronic graft-versus-host disease (GVHD), induced by injection of DBA/2 lymphocytes in (C57BL10*DBA/2) F 1 hybrids, develop a syndrome resembling systemic lupus erythematosus (SLE) with immune complex glomerulonephritis. In this model we evaluated the role of interactions between CD11a (LFA-1a) and CD54 (intercellular adhesion molecule-1 (ICAM-1)) molecules on leucocytes in the development of renal disease in systemic autoimmunity. Two weeks after induction of GVHD, when anti-nuclear autoantibodies were detected in the circulation and immune complexes had formed in the glomeruli, mice were injected twice per week with rat anti-CD11a and anti-CD54 MoAbs, or with their vehicle PBS, or with control rat IgG. MoAb treatment significantly lowered albuminuria and increased survival compared with control mice with GVHD. In the glomeruli of MoAb-treated mice there was markedly less binding of immunoglobulin and C3, while anti-renal tubular epithelium autoantibodies, but not anti-glomerular basement membrane autoantibodies, were significantly lowered in the circulation 4 weeks after disease induction. In addition, MoAb treatment inhibited the glomerular influx of CD11a + cells and decreased development of histological abnormalities in the kidneys. Both rat IgG-and MoAb-treated mice developed anti-rat immunoglobulin antibodies. Furthermore, a marked splenomegaly with an increase of the T cell compartment was observed in MoAb-treated mice with GVHD. These results show that CD11a/CD54 interactions are crucial for the full-blown development of lupus nephritis in this model. Treatment aimed at blocking the activity of these molecules profoundly attenuated the development of renal disease in chronic GVHD even if started when first symptoms of SLE (i.e. anti-nuclear autoantibodies in sera and glomerular binding of immunoglobulins) were already detectable.

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Section: Discussionsupporting

confidence: 86%

Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies

Kootstra

Giezen

Krieken

et al. 1997

Clinical and Experimental Immunology

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“…[8][9][10] Indeed, administration of monoclonal antibodies against adhesion molecules has been reported to prolong graft survival or induce tolerance. 13 We report a novel therapeutic strategy to attenuate acute rejection of heart allografts, utilizing ex vivo transfer of a 'decoy' cis element to bind the critical transcriptional factor NF B, thereby blocking the coordinated transactivation of the inflammatory genes involved in acute rejection. The specificity of the inhibi- tory effect of NF B decoy on acute rejection is supported by several points of evidence.…”

Section: Discussionmentioning

confidence: 99%

“…5,6,12 BALB/c (H-2 d ) mice hearts were transplanted into C3H/He (H-2 k ) mice as the major mismatch group for study of graft survival. 13 DBA/2 (H-2 d ) mice hearts were transplanted into B10.D2 (H-2 d ) mice as the minor mismatch group for pathological studies. 14 C3H/He mice hearts were transplanted into C3H/He mice as the isografts.…”

Section: Graft Survivalmentioning

confidence: 99%

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

et al. 2000

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Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NF B) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NF B decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NF B decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to

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“…Various immunosuppressive molecules have been tested in a variety of transplantation models and need to be assessed for their effectiveness on graft prolongation. In one of the strategies examined, the blockade of co-stimulatory signals by immunosuppressive proteins has been shown to prolong allograft survival in various transplantation settings [10,11]. In T cell-mediated immunity, the full activation of naïve T cells requires co-stimulatory signals generated by the ligation of CD28 on T cells with their receptor, B7-1/B7-2, on antigen-presenting cells (APCs) [12].…”

mentioning

confidence: 99%

Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion

et al. 2002

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Aims/hypothesis. This study examined whether locally expressed CTLA4-Ig can suppress the accelerated islet allograft rejection that is induced by donor-specific transfusion.Methods. CTLA4-Ig-transfected or parental MIN6 cells were transplanted subcutaneously into the right flank of streptozotocin-induced diabetic C3H/Hej mice with or without donor-specific transfusion. For donor-specific transfusion, spleen cells from C57BL/6 mice were injected i.v. at the time of transplantation. In other experiments, CTLA4-Ig-transfected and parental MIN6 cells were transplanted separately into each flank, together with donor-specific transfusion. Rejection was defined as a blood glucose concentration of more than 300 mg/dl in two consecutive measurements, and graft survival was confirmed by hyperglycaemia after the grafts were removed. The effect of an anti-CTLA4 antibody on the survival of CTLA4-Ig-transfected MIN6 cells was also examined.Results. In 7 of 12 donor-specific transfusion sensitised mice, CTLA4-Ig-transfected MIN6 cells remained viable 20 days after grafting, whereas all parental MIN6 cells (n = 10) were rejected promptly, within 14 days. The prolonged allograft survival was observed even in the absence of detectable levels of serum CTLA4-Ig, while the surviving allografts continued to produce CTLA4-Ig in situ. This protection was abrogated by an anti-CTLA4 antibody, but not by a control antibody. Furthermore, six animals that maintained normoglycaemia after the separate transplantation of parental and CTLA4-Ig-transfected MIN6 cells into each flank all showed abrupt hyperglycaemia after the CTLA4-Ig/MIN6 graft was removed, suggesting that this protection operated locally. Conclusion/interpretation. A beta-cell line genetically engineered to secrete CTLA4-Ig can protect a graft locally from the alloimmune response induced by donorspecific transfusion. [Diabetologia (2002) The insulin-secreting islets comprise only a small fraction of the whole pancreas (~1%); therefore, the transplantation of purified islets rather than the whole pancreas seems to be a reasonable approach to control metabolic dysfunction in patients with Type I (insulindependent) diabetes mellitus. Although the survival of vascularised pancreas allografts at one year has significantly improved following the introduction of T cellspecific immunosuppressants such as cyclosporin and FK506 [1], the survival of pancreatic islet grafts under the same immunosuppressive regimen is still under 30% one year after transplantation [2]. However, a current study reports that seven consecutive patients attained sustained insulin independence after pancreatic islet transplantation [3]. All these recipients were

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Specific Acceptance of Cardiac Allograft After Treatment with Antibodies to ICAM-1 and LFA-1

Cited by 694 publications

References 26 publications

Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies

Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

Locally expressed CTLA4-Ig in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion

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