December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
CD28 and CD154 Pathway Costimulatory Blockade Prolongs Corneal Allograft Survival
N Ardjomand; N Rogers; JC McAlister; PH Tan; AJ T George; FP Larkin
Author Affiliations & Notes
  • N Ardjomand
    Dept Ophthalmology Karl-Franzens-Univ Sch Med Graz Austria
  • N Rogers
    Dept of Immunology Imperial College School of Medicine London United Kingdom
  • JC McAlister
    Institute of Ophthalmology University College London London United Kingdom
  • PH Tan
    Dept of Immunology Imperial College School of Medicine London United Kingdom
  • AJ T George
    Dept of Immunology Imperial College School of Medicine London United Kingdom
  • FP Larkin
    Dept of Immunology Imperial College School of Medicine London United Kingdom
  • Footnotes
    Commercial Relationships   N. Ardjomand, None; N. Rogers, None; J.C. McAlister, None; P.H. Tan, None; A.J.T. George, None; F.P. Larkin, None. Grant Identification: Austrian Science Foundation J 1909 and NERC,UK
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2263. doi:
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      N Ardjomand, N Rogers, JC McAlister, PH Tan, AJ T George, FP Larkin; CD28 and CD154 Pathway Costimulatory Blockade Prolongs Corneal Allograft Survival . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2263.

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Abstract

Abstract: : Purpose: The costimulatory signals for T lymphocyte activation generated through CD80/86 and CD40 on APCs and their respective T cell surface ligands, CD28 and CD154 (CD40L), are each known to be functionally involved in allograft rejection. The effect of blockade of CD28 and/or CD154-mediated costimulation on mouse corneal allograft survival was investigated. Methods: Wild-type or BALB/c background CD28KO mice received C3H strain donor corneas. Graft recipients were treated with i.p. CTLA4-Ig and/or anti-CD154 (MR1) antibody on days 0, 2, 4 post-surgery. Graft survival was compared in treatment groups. Immunohistochemical examination on graft-infiltrating cells was performed following rejection. Results: Median survival time (MST) in untreated BALB/c recipients was 14d. Treatment with CTLA4-Ig, MR1, or both, extended median graft survival to 21, 25 and 29d respectively. MST was 28d in untreated CD28KO mice and 38d in MR1-treated mice, significantly longer than in wild-type. CTLA4-Ig treatment of CD28KO mice resulted in accelerated rejection (MST 16d). Phenotypes of graft-infiltrating T cells were found to be similar in all groups. Conclusion: Combinations of agents blocking the CD28 and CD154 costimulatory pathways have potential for prevention of rejection in clinical corneal transplantation.

Keywords: 433 immune tolerance/privilege • 435 immunomodulation/immunoregulation • 301 ACAID 
© 2002, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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