Prolongation of corneal allograft survival by an interleukin-2-immunoglobulin fusion protein in mice

Abstract 

· Background: Interleukin 2 (IL2) production by activated T-helper cells leads to activation and proliferation of cytotoxic T cells. Recently, an IL2-IgG fusion protein was found to suppress cell-mediated and humoral immune responses in mice. · Methods: We used the genetically engineered murine IL2-IgG2b fusion protein in a fully MHC-mismatched mouse keratoplasty model. The DTH reaction against sheep red blood cells was investigated as a measure of IL2-IgG2b-mediated immunosuppression. The animals were divided into three control groups (n≥6) [no treatment, subconjunctival (SQ) treatment with saline or mouse serum], two IL2 SQ-treated groups (14 μg or 140 μg), and four IL2-IgG2b-treated groups (14 μg, 140 μg or 280 μg SQ or 280 μg IP). · Results: Administration of 20 μg of IL2-IgG2b twice daily from the time of immunization until the time of challenge resulted in almost complete prevention of footpad swelling. The 140 μg SQ application of IL2 (allograft reaction on day 20.5 ± 4.04) and the 280 μg SQ (day 19.2 ± 2.48) or IP (day 19.7 ± 1.5) application of IL2-IgG2b fusion protein significantly prolonged the corneal graft survival in comparison to the untreated group (day 13.4 ± 1.35) (P<0.01) or saline control group (P<0.01) and the mouse-serum-treated group (day 14.7 ± 3.5) (P<0.05). · Conclusion: Our results indicate that, at a total dose of 280 μg, the fusion protein IL2-IgG2b causes no detectable side effects and very effectively suppresses the immune response of the corneal allograft in mice. This fusion protein could prove useful in the treatment of allograft rejections and autoimmune diseases.