Immunospecific suppression of encephalitogenic-activated T lymphocytes by chimeric cytotoxin IL-2-PE40.
We examined the action of a chimeric protein, IL-2-PE40, on the development of a T cell-mediated disease of the central nervous system with numerous similarities to multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). EAE is caused by IL-2 receptor-bearing T cells specific for myelin basic protein (BP). We report here that the treatment of Lewis rats with IL-2-PE40 delayed and shortened the course of EAE induced by BP in adjuvant and dramatically prevented EAE mediated by anti-myelin basic protein T line cells. The absence of paralytic signs, the absence of cell infiltration in the central nervous system, and the abatement of cellular immunity to myelin basic protein in the treated rats are direct consequences of the specific mechanism of action of IL-2-PE40. Our data support the notion that IL-2-PE40 may be efficient as an immunosuppressive agent for those disorders in which activated T cells play a crucial role.
Beraud
E
E
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
Lorberboum-Galski
H
H
Chan
C C
CC
FitzGerald
D
D
Pastan
I
I
Nussenblatt
R B
RB
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005098:Exotoxins / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007376:Interleukin-2 / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000276:immunology; D011550:Pseudomonas aeruginosa; D051381:Rats; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D007376:Interleukin-2; D004676:Myelin Basic Protein; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A