120 Brain Research, 489 (1989) 121)-128 Elsevier BRE 14543 Suppression of P2- T cell line-mediated experimental autoimmune neuritis by interleukin-2 receptor targeted monoclonal antibody ART 18" Hans-Peter Hartung 1, Bgrbel Sch~ifer 1, Tibor Diamantstein 2, Walter Fierz 3, Kurt Heininger I and Klaus V. Toyka ~ 1Department of Neurology, University of Diisseldorf, Dasseldorf (E R. G.), 2Institute of Immunology, Klinikum Steglitz, Free University of Berlin, West Berlin (ER. G.) and 3Division of Clinical Immunology, Department of Medicine, University of Zurich, Zurich (Switzerland) (Accepted 15 November 1988) Key words: Adoptive transfer-experimental autoimmune neuritis; Interleukin-2 receptor; Monoclonal antibody ART 18; Immunosuppression The monoclonal antibody ART 18 directed to the rat interleukin-2 receptor (IL-2 R) was administered to Lewis rats immediately prior to and/or on consecutive days after adoptive transfer of autoreactive Pz-T line lymphocytes. The effects of ART 18 and sham treatment on the development of adoptive transfer - - experimental autoimmune neuritis (AT-EAN) were assessed by clinical inspection, serial electrophysiological monitoring, and semiquantitative histomorphological analysis. Early injection of ART 18 suppressed AT-EAN while treatment after appearance of clinical signs did not. Since the IL-2 R is expressed exclusively on proliferating T cells activated by antigen, the in vivo application of an IL-2 R-targeted monoclonal antibody allows for more selective immunosuppression of experimental autoimmune disease of the peripheral nervous system than has previously been achieved. INTRODUCTION Since its description by Waksman and Adams in 195531 experimental autoimmune neuritis (EAN) has been recognized as an animal model of the acute Guillain-Barr6 syndrome 1'9'27. Attempts to pharma- cologically control this inflammatory demyelinating polyradiculoneuropathy have included the applica- tion of glucocorticosteroids 1°'15'19, cyclooxygenase inhibitors of arachidonic acid conversion 1°, the vasoactive amine-depleting agent reserpine 2, and cyclosporin A 8'18. In view of the role of T cells in the initiation of autoimmune diseases, monoclonal anti- bodies recognizing the CD4 molecule expressed on the surface of T helper/inducer cells were tried to influence the course of EAN and were shown to partially suppress the clinical signs and morpho- logical alterations typical of EAN in rat 5A4. While being effective this approach of immunomodulatory therapy may compromise the organism's capability of mounting protective immune reactions. To cir- cumvent these risks and achieve more selective immunosuppression, the monoclonal antibodies em- ployed should not be directed to differentiation antigens that are present on all T cells of a given subset but should rather target to activation markers expressed solely on cells that upon antigenic chal- lenge are undergoing a proliferative burst 3. Essen- tially all activated T lymphocytes expose on their surface a high-affinity receptor for the growth factor interleukin-2 (IL-2) as a consequence of antigenic stimulation whereas virtually none are displayed on resting T cells 3'29'32. In an attempt to effect more precisely targeted immunosuppression, we adminis- tered a monoclonal antibody against the T cell interleukin-2 receptor (IL-2 R) to rats with Pz- * Presented in part at the 8th Meeting of the Peripheral Nerve Study Group, OriUia, Ontario, August 24-27, 1987. Correspondence: H.-P. Hartung, Department of Neurology, University of Diisseldorf, Moorenstrasse 5, D-4000 Dfisseldoff, F.R.G. 0006-8993/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)