Corneal rat‐to‐mouse xenotransplantation and the effects of anti‐CD4 or anti‐CD8 treatment on cytokine and nitric oxide production

• Published in: Transplant international 2005-07, Vol.18 (7), p.854-862
• Main Authors: Pindjáková, Jana, Vítová, Andrea, Krulová, Magdaléna, Zajícová, Alena, Filipec, Martin, Holáň, Vladimír
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; anti‐CD4 treatment; Biological and medical sciences; CD4 Antigens - immunology; CD8 Antigens - immunology; Cornea - metabolism; Corneal Transplantation; corneal xenotransplantation; cytokines; Cytokines - biosynthesis; Female; Gene Expression; General aspects; graft survival; Graft Survival - drug effects; Male; Medical sciences; Mice; Mice, Inbred BALB C; Nephrology. Urinary tract diseases; nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Pharmacology. Drug treatments; Rats; Rats, Inbred Lew; Transplantation, Heterologous
• ISSN: 0934-0874; 1432-2277
• DOI: 10.1111/j.1432-2277.2005.00112.x

Summary 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, γ‐interferon (IFN‐γ) 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‐γ and iNOS and with NO production.