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Inhibition of corneal allograft reaction by CTLA4-Ig

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Abstract

• Background: Activation of T cells requires both the interaction of T-cell receptor with major histocompatibility complex on the antigen-presenting cell and costimulatory signals, for instance the B7 antigens expressed on antigen-presenting cells and the CD28 molecule expressed on T cells. A recombinant fusion protein, CTLA4-Ig, has been produced that contains the extracellular domain of human CTLA4 fused to IgGl constant region and that binds the B7 molecule with high affinity. Blocking the CD28/B7 interaction with CTLA4-Ig inhibits T cell activation in vitro and in vivo. • Methods: We used CTLA4-Ig in a fully MHC-mismatched mouse keratoplasty model. The animals were divided into four groups: (1) no treatment, (2) intraperitoneal treatment with 130 μg CTLA4-Ig, (3) intraperitoneal treatment with 300 μg CTLA4-Ig, (4) subconjunctival treatment with 290 μg CTLA4-Ig. • Results: The allograft reaction occurred in untreated animals between days 12 and 16 (mean 13.5). While topical application of CTLA4-Ig seemed to shorten the graft survival (mean 11.6 days) and systemic application of 130 μg had no influence (mean 14.0), only intraperitoneal injection of 300 μg of CTLA4-Ig prolonged the survival of allografts (mean >20 days) (P<0.01). • Conclusion: CTLA4-Ig prolonged significantly the survival of corneal allografts in a fully MHC-mismatched mouse keratoplasty model, but the small antigen load of the corneal transplant and the anterior chamber-associated immune deviation (ACAID) may have a disadvantage to induce tolerance in this model of CTLA4-Ig therapy.

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Authors and Affiliations

  1. Department of Ophthalmology, Benjamin Franklin Medical Center, Free University of Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Friedrich Hoffmann, Er-Ping Zhang & Joachim Wachtlin

  2. Institute of Immunology, Benjamin Franklin Medical Center, Free University of Berlin, Berlin, Germany

    Thomas Pohl & Silvia Bulfone-Paus

  3. Department of Internal Medicine and Nephrology Benjamin Franklin Medical Center, Free University of Berlin, Berlin, Germany

    Ulrich Kunzendorf

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  1. Friedrich Hoffmann
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  2. Er-Ping Zhang
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  4. Ulrich Kunzendorf
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  6. Silvia Bulfone-Paus
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Correspondence to Friedrich Hoffmann.

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Hoffmann, F., Zhang, EP., Pohl, T. et al. Inhibition of corneal allograft reaction by CTLA4-Ig. Graefe's Arch Clin Exp Ophthalmol 235, 535–540 (1997). https://doi.org/10.1007/BF00947013

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  • DOI: https://doi.org/10.1007/BF00947013

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