T-CELL DIRECTED IMMUNOTHERAPY OF INFLAMMATORY DEMYELINATION IN THE PERIPHERAL NERVOUS-SYSTEM - POTENT SUPPRESSION OF THE EFFECTOR PHASE OF EXPERIMENTAL AUTOIMMUNE NEURITIS BY ANTI-CD2 ANTIBODIES

Experimental autoimmune neuritis (EAN) of Lewis rats, an inflammatory demyelinating neuropathy and model of the human Guillain-Barre syndrom e (GBS), was used to evaluate the novel T cell directed immunotherapy with the anti-CD2 monoclonal antibody (mAb) OX34. Clinical signs of EA N actively induced by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA) were totally prevented or markedl y suppressed by preventative injections of OX34 starting 8 days post-i mmunization (p.i.). Moreover therapeutic application of the mAb beginn ing on the day of first clinical signs of EAN markedly inhibited progr ession of disease. Electrophysiological and histological investigation of sciatic nerves 17 and 18 days p.i., respectively, also revealed an inhibitory effect of OX34 on EAN-associated functional and morphologi cal nerve damage. Similarly, therapeutic injections of OX34 after onse t of EAN actively induced by immunization with a neuritogenic peptide of the P-2 protein completely halted further deterioration of clinical disease. Finally, clinical, electrophysiological and histological sig ns of adoptive transfer EAN mediated by injection of neuritogenic T he lper line cells were prevented or strongly suppressed by OX34-applicat ion on the day of cell transfer and 4 days later underlining the impac t of the mAb on the effector phase of the disease. Since the anti-CD2 mAb did not exert its effect by inhibition of T cell activation induct ion of anergy, modulation of CD2 antigens, or by T cell depletion, we assume that it may affect migration of T lymphocytes across the blood- nerve barrier The immediate and marked suppression of ongoing EAN by t he mAb lead to the recommendation of anti-CD2 mAbs as candidates for T cell directed immunotherapy of the GBS.