The suppressive effect of an antibody to the alpha beta cell receptor in rat adjuvant arthritis: studies on optimal treatment protocols.
An antibody (R73) to the alpha beta T cell receptor (TCR) was able to dramatically suppress adjuvant arthritis (AA) in rats. The efficacy of R73 treatment was investigated with regard to antibody dosage, injection route and timing of injections. R73 was equally effective in reducing joint swelling throughout a wide dose range (80 to 2000 microgram/dose) when given on day 15, 18, and 21 after arthritis induction. Both i.p. and i.v. injection were able to suppress the pre-existing joint swelling to the same extent. However, R73 was only effective when given before or at the peak of joint swelling which occurred between day 18 to 24. Synovial membrane hyperplasia, mononuclear cell infiltration as well as cartilage and bone destruction were markedly reduced after therapy. The effect of R73 was associated with depletion of alpha beta+ T cells from the circulation even at low antibody doses. Only few alpha beta+ T cells were found in the pannus tissue. Late treatment on day 27, 30 and 33 after arthritis induction did not influence clinical scoring of the disease and histological examination thereafter did not show any difference between treated animals and controls. We conclude that antibody therapy directed at the TCR seems to be very effective even in pre-existing autoimmune diseases if the relevant T cell population is affected. However, inflammation and joint destruction may reach a state at which anti-TCR treatment is no longer effective.
Yoshino
S
S
Max-Planck-Society, Institute for Clinical Immunology, Universität Erlangen-Nürnberg, FRG.
Kinne
R
R
Hünig
T
T
Emmrich
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D006614:Hindlimb / Q000473:pathology; D006801:Humans; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D016693:Receptors, Antigen, T-Cell, alpha-beta
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta