Inhibition of corneal allograft reaction by CTLA4-Ig
Autor: | Ulrich Kunzendorf, Silvia Bulfone-Paus, Joachim Wachtlin, Er-Ping Zhang, Thomas Pohl, Friedrich Hoffmann |
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Rok vydání: | 1997 |
Předmět: |
Graft Rejection
Immunoconjugates Recombinant Fusion Proteins T cell medicine.medical_treatment Intraperitoneal injection chemical and pharmacologic phenomena Pharmacology Major histocompatibility complex Abatacept Corneal Transplantation Major Histocompatibility Complex Mice Cellular and Molecular Neuroscience Antigen Antigens CD medicine Animals Humans Transplantation Homologous CTLA-4 Antigen Mice Inbred BALB C Mice Inbred C3H biology Drug Administration Routes Graft Survival CD28 Corneal Transplant Immunotherapy Antigens Differentiation Sensory Systems Ophthalmology medicine.anatomical_structure Immunology biology.protein Female Antibody Immunosuppressive Agents Follow-Up Studies |
Zdroj: | Graefe's Archive for Clinical and Experimental Ophthalmology. 235:535-540 |
ISSN: | 1435-702X 0721-832X |
DOI: | 10.1007/bf00947013 |
Popis: | • 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 |
Databáze: | OpenAIRE |
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