Interleukin-2 Pseudomonas exotoxin chimeric protein is cytotoxic to B cell cultures derived from myasthenia gravis patients.
IL-2-PE664Glu is a chimeric cytotoxin consisting of interleukin-2 (IL-2) fused to a mutant form of Pseudomonas exotoxin (PE664Glu). The chimeric cytotoxin has been previously shown to be extremely toxic to both phytohaemagglutinin blasts and mixed leukocyte reaction blasts prepared from monkey and human lymphocytes. To explore the possible clinical utility of IL-2-PE664Glu for autoimmune diseases, particularly in which B cells are involved, we tested the sensitivity of B cell lines derived from myasthenia gravis patients to this chimeric cytotoxin. 65% (15 out of 23) of the tested B cell lines were sensitive to IL-2-PE664Glu mediated cytotoxicity. B cell lines from control donors as well as from patients with another autoimmune disease, multiple sclerosis, were much less sensitive to IL-2-PE664Glu cytotoxicity. Moreover, a control protein lacking the IL-2 as the targeting moiety of the chimera, had no effect toward all B cell lines tested, thus establishing its specific activity. A detailed study of the IL-2 receptor of the patients' B cells, using the PCR technique and FACS analysis, showed that the cells express mainly the beta and gamma chains and at a lower level also the alpha-chain of the IL-2 receptor. Our results suggest that IL-2-PE664Glu could be effective for selective targeted immunotherapy of myasthenia gravis patients.
Steinberger
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I
Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Brenner
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T
Lorberboum-Galski
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H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000187:drug effects*; D001426:Bacterial Proteins / Q000633:toxicity*; D001483:Base Sequence; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D005098:Exotoxins / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000235:genetics; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins / Q000633:toxicity
D001426:Bacterial Proteins; D005098:Exotoxins; D007376:Interleukin-2; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C065698:interleukin 2-PE66(4Glu) protein, recombinant