Therapeutic effects of monoclonal antibodies to alpha beta TCR but not to CD4 on collagen-induced arthritis in the rat.
The role which T cells play in the pathogenesis of the collagen-induced arthritis (CIA) model is not yet fully understood. Although CIA is most likely dependent on the activity of class II-restricted CD4+ T cells, only prophylactic but not therapeutic anti-CD4 treatments have been successful. The lack of therapeutically effective anti-T cell monoclonal antibody treatments has questioned the importance of T cells in ongoing CIA. However, recently we found that ongoing CIA in DA rats induced with homologous CII can be suppressed by injections with an anti-alpha beta TCR antibody. Having a CIA model where ongoing disease was clearly dependent on T cells, we addressed in the present work whether also an anti-CD4 treatment could suppress ongoing arthritis in this model. Although no CD4hi lymph node cells were seen after an anti-CD4 injection, the arthritis was suppressed only after treatment at immunization but not after treatment just before onset of disease. In comparison, the anti-TCR treatment at the time of onset was clearly suppressive even though a large fraction of the T cells was not depleted. This indicates that the different outcome of the anti-TCR and anti-CD4 treatment was not due to a different capacity to deplete T cells in vivo.
Goldschmidt
T J
TJ
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Holmdahl
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001168:Arthritis / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003094:Collagen / Q000276:immunology; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen