Interleukin 2-diphtheria toxin fusion protein can abolish cell-mediated immunity in vivo.
De novo expression of the interleukin 2 receptor (IL-2R) is a critical and pivotal event in initiation of an immune response. Targeting the low-affinity IL-2-binding p55 subunit of the high-affinity IL-2R with the rat anti-mouse IgM monoclonal antibody M7/20 suppresses a variety of T-cell-mediated reactions, including transplant rejection, autoimmunity, and delayed-type hypersensitivity (DTH). A hybrid IL-2-toxin gene was constructed from the diphtheria toxin gene by replacing the DNA encoding the diphtheria toxin receptor-binding domain with the DNA encoding the receptor-binding domain of IL-2, and the fusion protein encoded by the hybrid gene was expressed in Escherichia coli [Williams, D.P., Parker, K., Bacha, P., Bishai, W., Borowski, M., Genbauffe, F., Strom, T.B. & Murphy, J.R. (1987) Protein Eng. 1, 493-498]. We examined the action of the chimeric IL-2-toxin fusion protein on an in vivo T-cell mediated response, DTH. The IL-2-toxin fusion protein was found to be a potent immunosuppressive agent. Treatment of mice with the IL-2-toxin blocks DTH and prevents expansion of IL-2R+ T cells. Indeed, IL-2-toxin treatment targets IL-2R+ T cells in vivo and is shown to selectively eliminate their appearance in draining lymph nodes. DTH suppression was observed even in mice possessing high titers of antibodies to diphtheria toxoid.
D000818:Animals; D004167:Diphtheria Toxin / Q000008:administration & dosage*; D004168:Diphtheria Toxoid / Q000276:immunology; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D000922:Immunotoxins / Q000633:toxicity*; D007376:Interleukin-2 / Q000008:administration & dosage; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects*
D004167:Diphtheria Toxin; D004168:Diphtheria Toxoid; D000922:Immunotoxins; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2