IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Comer, R. M.
Right arrow Articles by Larkin, D. F. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Comer, R. M.
Right arrow Articles by Larkin, D. F. P.
(Investigative Ophthalmology and Visual Science. 2002;43:1095-1103.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

Effect of Administration of CTLA4-Ig as Protein or cDNA on Corneal Allograft Survival

Richard M. Comer1, William J. King1, Navid Ardjomand1, Stefanos Theoharis1, Andrew J. T. George1 and D. Frank P. Larkin1,2

1 From the Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, United Kingdom; and 2 Moorfields Eye Hospital, London, United Kingdom.

PURPOSE. To examine the role of the CD28–CD80–CD86 pathway of T-lymphocyte costimulation in corneal allograft rejection and the effect of blockade of that pathway on graft survival.

METHODS. Kinetics of CD80 and CD86 expression in the cornea and draining lymph nodes were examined by RT-PCR and immunohistochemistry in untreated allograft recipients in a high-responder rat model. The effect of blockade of CD28-mediated costimulation was first examined by ex vivo incubation of excised Brown Norway rat donor cornea with the inhibitory protein CTLA4-Ig or an adenovirus vector (AdCTLA) expressing CTLA4-Ig, before grafting into Lewis rat recipients. A second group of graft recipients received systemic posttransplantation treatment with either CTLA4-Ig or AdCTLA.

RESULTS. Expression of CD80 mRNA was increased in both donor and recipient cornea 16 hours after transplantation, whereas CD86 was detected constitutively, with no significant early increase. Immunohistochemistry on day 5 after transplantation demonstrated major histocompatibility complex (MHC) class II expression, no CD80, and only a trace of CD86 in corneal allografts. In lymph nodes strong MHC class II, weak CD80, and moderate CD86 expression was noted. Both donor cornea and recipient treatment with CTLA4-Ig resulted in prolonged allograft survival. AdCTLA was found to induce sustained secretion of bioactive CTLA4-Ig from corneas infected ex vivo. Survival of corneal allografts incubated with AdCTLA was marginally prolonged, and systemic treatment with AdCTLA significantly prolonged survival.

CONCLUSIONS. Protein- or gene-based administration of CTLA4-Ig prolongs allograft survival by treatment of either the recipient or the donor tissue ex vivo before grafting.




This article has been cited by other articles:


Home page
 IOVSHome page
N. Gong, U. Pleyer, K. Vogt, I. Anegon, A. Flugel, H.-D. Volk, and T. Ritter
Local Overexpression of Nerve Growth Factor in Rat Corneal Transplants Improves Allograft Survival
Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1043 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. P. Watson, A. J. T. George, and D. F. P. Larkin
Differential effects of costimulatory pathway modulation on corneal allograft survival.
Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3417 - 3422.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Klebe, D. J. Coster, P. J. Sykes, S. Swinburne, P. Hallsworth, J.-P. Y. Scheerlinck, R. Krishnan, and K. A. Williams
Prolongation of Sheep Corneal Allograft Survival by Transfer of the Gene Encoding Ovine IL-12-p40 but Not IL-4 to Donor Corneal Endothelium
J. Immunol., August 15, 2005; 175(4): 2219 - 2226.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
T Ritter, N Gong, and U Pleyer
Is ex vivo adenovirus mediated gene transfer a therapeutic option for the treatment of corneal diseases?
Br. J. Ophthalmol., June 1, 2005; 89(6): 648 - 649.
[Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
C F Jessup, H M Brereton, D J Coster, and K A Williams
In vitro adenovirus mediated gene transfer to the human cornea
Br. J. Ophthalmol., June 1, 2005; 89(6): 658 - 661.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
C. F. Jessup, H. M. Brereton, P. J. Sykes, M. A. Thiel, D. J. Coster, and K. A. Williams
Local Gene Transfer to Modulate Rat Corneal Allograft Rejection
Invest. Ophthalmol. Vis. Sci., May 1, 2005; 46(5): 1675 - 1681.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
N. Ardjomand, J. C. McAlister, N. J. Rogers, P. H. Tan, A. J. T. George, and D. F. P. Larkin
Modulation of Costimulation by CD28 and CD154 Alters the Kinetics and Cellular Characteristics of Corneal Allograft Rejection
Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 3899 - 3905.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the Association for Research in Vision and Ophthalmology