Prolongation of corneal allograft survival by an interleukin-2-immunoglobulin fusion protein in mice.
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 > or = 6) [no treatment, subconjunctival (SQ) treatment with saline or mouse serum], two IL2 SQ-treated groups (14 micrograms or 140 micrograms), and four IL2-IgG2b-treated groups (14 micrograms, 140 micrograms or 280 micrograms SQ or 280 micrograms i.p.).


RESULTS
Administration of 20 micrograms 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 micrograms SQ application of IL2 (allograft reaction on day 20.5 +/- 4.04) and the 280 micrograms SQ (day 19.2 +/- 2.48) or i.p. (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).


CONCLUSIONS
Our results indicate that, at a total dose of 280 micrograms, 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.
Department of Ophthalmology, Benjamin Franklin Medical Center, Free University of Berlin, Germany.
E P
EP
Zhang
T
T
Pohl
S
S
Bulfone-Paus
J
J
Wachtlin
U
U
Kunzendorf
F
F
Hoffmann
D000818:Animals; D016039:Corneal Transplantation / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins