Inhibition of corneal allograft reaction by CTLA4-Ig

Autor: Ulrich Kunzendorf, Silvia Bulfone-Paus, Joachim Wachtlin, Er-Ping Zhang, Thomas Pohl, Friedrich Hoffmann
Rok vydání: 1997
Předmět:
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