65-kD PROTEIN PROTECTS AGAINST ARTHRITIS

Arguments for an involvement of bacteria in the pathogenesis ofchronicjoint inflammation (arthritis) are several (1-12). To study the pathogenetic mechanism ofbacteriuminduced sterile arthritis, different animal models are used, among which, Mycobacterium tuberculosis-induced or adjuvant arthritis (AA)t (2) and streptococcal cell wall (SCW)-induced arthritis (1) are the best known. In both models, bacterium-specific T lymphocytes have been demonstrated to play a crucial role (13-24, and van den Broek, M. F, M. C. J. van Bruggen, A. J. Severijnen, andW B. van den Berg, manuscript submitted for publication), andone aspect ofthis role might be the crossreactive nature ofthese T lymphocytes to cartilage-associated components (22, 25). In AA it is a well known fact that rats that have recovered from arthritis are resistant to a subsequent induction of AA (17, 18), and it has been demonstrated recently that pretreatment ofrats with the mycobacterial 65-kD protein resulted in the same resistance to AA when tested 35 d later (13) . Since the 65-kD protein is an ubiquitous bacterial common antigen (26), with a homologous molecule present also in streptococci, and probably even associated with cell walls (27), we tested the effects ofpretreatment with the mycobacteria165-kD protein on the development of SCW arthritis . Here we show that intraperitoneal administration of 50 lAg 65-kD protein to rats 35, 25, 15, or even as short as 5 d before induction of SCW arthritis completely protected the rats against the chronic erosive polyarthritis . The resistance against SCW arthritis is transferrable by spleen T cells to naive recipients . The protection coincides with a suppression of SCW-specific T cell responses, thus displaying features much alike suppression or tolerance leading to resistance in other models for autoimmune diseases (28-31).