MEDIATORS AND AUTOPATHOGENIC EFFECTOR-CELLS IN PROTEOGLYCAN-INDUCED ARTHRITIC AND CLINICALLY ASYMPTOMATIC BALB C MICE/

Proteoglycan (aggrecan)-induced arthritis is an autoimmune inflammator y animal model produced in genetically susceptible BALB/c mice. This a nimal model shows many similarities to human rheumatoid arthritis as i ndicated by clinical assessments, histopathological studies, and immun ological parameters. The systemic immunization of mice with a select g roup of cartilage proteoglycans provokes immune responses to the immun izing antigen and then the production of cross-reactive antibodies to self proteoglycans. This is followed by an explosive proliferation of autoreactive T cells, especially in joint draining lymph nodes, accomp anied by local (joint) inflammatory events. In the current experiments we found that lymphocytes from arthritic, or potentially arthritic bu t yet clinically asymptomatic animals, produced more IL-2 than those T cells obtained from animals immunized with nonarthritogenic PGs. In a ddition, synoviocytes isolated from prearthritic or arthritic animals produced several-fold more interleukin-1 beta (IL-1 beta) than cells f rom normal animals. Flow cytometric analysis indicated an autoantigen (mouse PG)-specific selective proliferation of surface Ig(+)/CD45R(+) cells in prearthritic stages followed by the proliferation of predomin antly T helper (CD4(+)) cells during and after the development of arth ritis. (C) 1994 Academic Press, Inc.