Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Comer, RM; King, WJ; Ardjomand, N; Theoharis, S; George, AJ; Larkin, DF.
Effect of administration of CTLA4-Ig as protein or cDNA on corneal allograft survival.
Invest Ophthalmol Vis Sci. 2002; 43(4):1095-1103
[OPEN ACCESS]
Web of Science
PubMed
- Autor*innen der Med Uni Graz:
- Ardjomand Navid
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenoviridae - genetics
- Animals - genetics
- Antigens, CD - genetics
- Antigens, CD28 - genetics
- Antigens, CD80 - genetics
- Antigens, CD86 - genetics
- Antigens, Differentiation - administration and dosage
- Cornea - metabolism
- Corneal Transplantation - metabolism
- DNA, Complementary - administration and dosage
- Female - administration and dosage
- Gene Therapy - administration and dosage
- Genetic Vectors - administration and dosage
- Graft Survival - drug effects
- Immunoconjugates - drug effects
- Immunoenzyme Techniques - drug effects
- Immunoglobulin Fc Fragments - drug effects
- Immunosuppressive Agents - administration and dosage
- Lymph Nodes - metabolism
- Membrane Glycoproteins - genetics
- RNA, Messenger - metabolism
- Rats - metabolism
- Rats, Inbred BN - metabolism
- Rats, Inbred Lew - metabolism
- Recombinant Fusion Proteins - metabolism
- Reverse Transcriptase Polymerase Chain Reaction - metabolism
- Transplantation, Homologous - metabolism