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.