INTERLEUKIN-2 PSEUDOMONAS EXOTOXIN CHIMERIC PROTEIN IS CYTOTOXIC TO B-CELL CULTURES DERIVED FROM MYASTHENIA-GRAVIS PATIENTS

IL-2-PE66(4Glu) is a chimeric cytotoxin consisting of interleukin-2 (I L-2) fused to a mutant form of Pseudomonas exotoxin (PE66(4Glu)). The chimeric cytotoxin has been previously shown to be extremely toxic to both phytohaemagglutinin blasts and mixed leukocyte reaction blasts pr epared from monkey and human lymphocytes. To explore the possible clin ical utility of IL-2-PE66(4Glu) for autoimmune diseases, particularly in which B cells are involved, we tested the sensitivity of B cell lin es 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- PE66(4Glu) mediated cytotoxicity. B cell lines from control donors as well as from patients with another autoimmune disease, multiple sclero sis, were much less sensitive to IL-2-PE66(4Glu) cytotoxicity. Moreove r, a control protein lacking the IL-2 as the targeting moiety of the c himera, had no effect toward all B cell lines tested, thus establishin g its specific activity. A detailed study on the IL-2 receptor of the patients' B cells, using the PCR technique and FAGS analysis, showed t hat 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 t hat IL-2-PE66(4Glu) could be effective for selective targeted immunoth erapy of myasthenia gravis patients.