Treatment of corneal allograft rejection with the cytotoxin IL-2-PE40.
IL-2-PE40 is a recombinant chimeric protein composed of IL-2, fused to a modified pseudomonas exotoxin. This molecule is extremely toxic to activated T cells expressing high-affinity IL-2R. We used this new molecule for selective immunosuppression to treat corneal allograft rejection in the rat, using Fisher and Lewis rats, a strain combination differing only in medial and minor histocompatibility antigens. The effect of IL-2-PE40 on the immunologic response was studied using both a heterotopic corneal graft model and orthotopic grafts. At the dose of 0.31 micrograms/g given intraperitoneally every 12 hr, IL-2-PE40 produced a significant reduction of both total lymph node cells and cytotoxic-T-cell (CTL) activity in draining lymph nodes (DLN) of heterotopically grafted animals. IL-2-PE40 treatment also significantly reduced the clinical rejection score and cumulative rejection rate (CRR) in orthotopic grafts and appears to be a very effective immunosuppressive agent.
Herbort
C P
CP
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
de Smet
M D
MD
Roberge
F G
FG
Nussenblatt
R B
RB
FitzGerald
D
D
Lorberboum-Galski
H
H
Pastan
I
I
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D016039:Corneal Transplantation; D003524:Cyclosporins / Q000627:therapeutic use; D005098:Exotoxins / Q000494:pharmacology*; D006084:Graft Rejection / Q000187:drug effects*; D000922:Immunotoxins / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016042:Transplantation, Heterotopic
D001426:Bacterial Proteins; D003524:Cyclosporins; D005098:Exotoxins; C057961:IL-2-PE40 chimeric protein, recombinant; D000922:Immunotoxins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins