Prevention and therapy of experimental autoimmune neuritis by an antibody against T cell receptors-alpha/beta.
The mAb R73 directed to the TCR-alpha/beta of rat lymphocytes was tested for its therapeutic potential during the effector phase of experimental autoimmune neuritis (EAN) in Lewis rats. EAN can be actively induced by immunization with bovine peripheral nerve myelin, bovine P2 protein, or a peptide containing its neuritogenic epitope and serves as a model of the human Guilain-Barré syndrome. Adoptive transfer of activated P2-specific T lymphocytes also produces the monophasic disease (AT-EAN) characterized by inflammation and demyelination of peripheral nerves and highlights the central role of T lymphocytes in the pathogenesis of EAN. A single administration of the mAb R73 immediately after injection of activated P2-specific T line cells completely prevented the development of clinical and electrophysiologic signs of EAN in most animals and greatly alleviated the disease in the others. In further experiments mAb R73 was applied after the appearance of first clinical signs of EAN actively induced by immunization with a neuritogenic peptide or bovine peripheral nerve myelin. In both cases the anti-TCR-alpha/beta mAb reversed clinical signs of EAN and prevented the development of peripheral nerve dysfunction. In vivo and in vitro data suggest that impairment of Ag recognition and T cell function by occupancy of the TCR and R73-induced TCR-modulation rather than depletion of TCR-alpha/beta-bearing lymphocytes is the decisive mechanism underlying suppression of EAN that is apparent already within 48 h of the first R73 injection.
Jung
S
S
Department of Neurology, University of Würzburg, Germany.
Krämer
S
S
Schluesener
H J
HJ
Hünig
T
T
Toyka
K
K
Hartung
H P
HP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003711:Demyelinating Diseases / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D004705:Endocytosis; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods; D007167:Immunotherapy; D004676:Myelin Basic Protein / Q000276:immunology; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta