Selective immunosuppression of activated T cells with the chimeric toxin IL-2-PE40. Inhibition of experimental autoimmune uveoretinitis

• Published in: The Journal of immunology (1950) Vol. 143; no. 11; pp. 3498 - 3502
• Main Authors: Roberge, FG, Lorberboum-Galski, H, Le Hoang, P, de Smet, M, Chan, CC, Fitzgerald, D, Pastan, I
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.12.1989
• Subjects: ADP Ribose Transferases; Animals; Autoantibodies - biosynthesis; Autoimmune Diseases - etiology; Autoimmune Diseases - immunology; Bacterial Toxins; Cell Line; Chimera; Exotoxins - pharmacology; Humans; Immunosuppressive Agents - pharmacology; Immunotoxins - pharmacology; Interleukin-2 - pharmacology; Lymphocyte Activation - drug effects; Lymphocyte Depletion; Male; Pseudomonas; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa Exotoxin A; Rats; Rats, Inbred Lew; Recombinant Fusion Proteins - pharmacology; Retinitis - etiology; Retinitis - immunology; Virulence Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.143.11.3498

A characteristic of activated T lymphocytes is the expression of high affinity IL-2R. We studied a new method of selective immunosuppression directed against activated T cells by using a chimeric recombinant protein (IL-2-PE40) composed of IL-2 fused to a modified Pseudomonas exotoxin lacking its cell recognition domain. As a model of T cell-mediated disease, we used experimental autoimmune uveoretinitis (EAU) produced in Lewis rats by active immunization with the retinal S-Ag. The treatment protocol consisted of i.p. injection of IL-2-PE40 at 0.25 micrograms/g every 12 h. Controls were PBS, PE40, or IL-2-PE40asp553 a mutant form of the molecule with reduced activity. Treatment with IL-2-PE40 resulted in a significant reduction of the incidence and severity of EAU over controls. The analysis of the effect of i.p. injection of IL-2-PE40 on the popliteal draining lymph nodes of immunized animals showed a marked reduction in the lymphocytes content. Transfer experiments demonstrated that IL-2-PE40 prevented the development of EAU effector T cells. Interestingly, although activated B cells were reported to express IL-2R, there was no significant reduction of antibody production against the immunizing Ag under IL-2-PE40 treatment, suggesting sparing of the B cells.