Effect of administration of CTLA4-Ig as protein or cDNA on corneal allograft survival.
Invest Ophthalmol Vis Sci
; 43(4): 1095-103, 2002 Apr.
Article
em En
| MEDLINE
| ID: mdl-11923251
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos de Diferenciação
/
Transplante de Córnea
/
DNA Complementar
/
Imunoconjugados
/
Córnea
/
Sobrevivência de Enxerto
/
Imunossupressores
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article