TREATMENT OF A NEWLY ESTABLISHED TRANSGENIC MODEL OF CHRONIC ARTHRITIS WITH NONDEPLETING ANTI-CD4 MONOCLONAL-ANTIBODY

We established a novel animal model for rheumatoid arthritis (RA) by f ollowing backcrossing to DBA/1 of (SWR/J x DBA/1)F-1 TCR-beta Tg mice, previously reported to be highly susceptible to collagen-induced arth ritis, These mice evolved, upon collagen type II immunization, into a chronic arthritis that histopathologically resembles RA, The availabil ity of such a model prompted us to study the role of CD4(+) T cells th roughout the evolution of disease, Here, we show that administration o f nondepleting anti-CD4 not only prevented the evolution of disease bu t also treated established arthritis, Moreover, functional analyses of T cells isolated from anti-CD4-treated mice demonstrated that the mec hanism of protection is not achieved by suppression of the Th1 populat ion but is mediated by induction of collagen type II-specific T cell a nergy, Our study suggests that: 1) CD4(+) T cells have a fundamental r ole both in the induction and in the perpetuation of disease; 2) targe ting T cells may be an appropriate therapeutic option; and 3) a suitab le and well-balanced anti-CD4 treatment may be a valid approach to the control of RA.