EXACERBATION OF ESTABLISHED COLLAGEN-INDUCED ARTHRITIS IN MICE TREATED WITH AN ANTI-T CELL-RECEPTOR ANTIBODY

Objective. To investigate the effect of T cell depletion on establishe d collagen-induced arthritis (CIA) in mice, using monoclonal antibodie s (MAb) to T cell receptor alpha/beta (TCR alpha/beta). In addition, e xperiments using anti-CD3 MAb were performed for comparison. Methods. CIA was induced in male DBA/1 mice by immunizing them twice with bovin e type II collagen (CII). The arthritis score and anti-CII antibody ti ters were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells. Results. When anti-TCR alpha/beta MAb was inj ected on the day of CII priming, no arthritis was detected in associat ion with depressed anti-CII antibody titers. Unexpectedly, however, wh en MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints . Anti-CII antibody titers were not affected. The addition of anti-TCR gamma/delta MAb had no effect on the augmented arthritis. T cell depl etion by anti-CD3 MAb during established CIA also caused an enhancemen t of arthritis, which was, however, weak and only transient. FACS anal ysis revealed that the early improvement of arthritis after the transi ent augmentation seen in the mice treated with anti-CD3 MAb paralleled the early recovery of alpha/beta T cells in the periphery.