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-Barré syndrome (GBS), was used to evaluate the novel T cell directed immunotherapy with the anti-CD2 monoclonal antibody (mAb) OX34. Clinical signs of EAN actively induced by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA) were totally prevented or markedly suppressed by preventative injections of OX34 starting 8 days post-immunization (p.i.). Moreover, therapeutic application of the mAb beginning on the day of first clinical signs of EAN markedly inhibited progression 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 morphological nerve damage. Similarly, therapeutic injections of OX34 after onset of EAN actively induced by immunization with a neuritogenic peptide of the P2 protein completely halted further deterioration of clinical disease. Finally, clinical, electrophysiological and histological signs of adoptive transfer EAN mediated by injection of neuritogenic T helper line cells were prevented or strongly suppressed by OX34-application on the day of cell transfer and 4 days later, underlying the impact 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, induction 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 the mAb lead to the recommendation of anti-CD2 mAbs as candidates for T cell directed immunotherapy of the GBS.
Jung
S
S
Department of Neurology, Universität Würzburg, Germany.
Toyka
K
K
Hartung
H P
HP
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D002417:Cattle; D003711:Demyelinating Diseases / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000628:therapy; D011129:Polyradiculoneuropathy / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors