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 CD4(hi) 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. (C) 1994 Academic Press, Inc.