Corneal rat-to-mouse xenotransplantation and the effects of anti-CD4 or anti-CD8 treatment on cytokine and nitric oxide production.
Corneal xenotransplantation may be an alternative approach to overcome shortage of allografts for clinical transplantation. Orthotopic corneal rat-to-mouse xenotransplantation and syngeneic transplantation was performed and the effects of anti-CD4 and anti-CD8 treatments on corneal xenograft survival and production of cytokines, interleukin (IL)-2, IL-4, IL-10, gamma-interferon (IFN-gamma) and nitric oxide (NO) were evaluated. RT-PCR was used to determine the expression of genes for cytokines and inducible nitric oxide synthase (iNOS) in the grafts. The presence of iNOS protein in grafts was detected by immunofluorescent staining. We found that corneal xenotransplantation was associated with a strong upregulation of genes for both Th1 and Th2 cytokines and with NO production in the graft. Treatment of xenograft recipients with mAb anti-CD4, but not anti-CD8, resulted in a profound inhibition of IL-2, IL-4 and IL-10 production, and in a significant prolongation of corneal xenograft survival. The results show that upregulation of Th2 cytokines after corneal xenotransplantation does not correlate with xenograft rejection. Rather, corneal graft rejection is associated with the expression of genes for IFN-gamma and iNOS and with NO production.
Pindjáková
Jana
J
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Vítová
Andrea
A
Krulová
Magdaléna
M
Zajícová
Alena
A
Filipec
Martin
M
Holán
Vladimír
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D003315:Cornea / Q000378:metabolism; D016039:Corneal Transplantation; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006085:Graft Survival / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat