Abstract. We have been studying the pathogenesis of adjuvant arthritis in rats using a long-term cell line of T lymphocytes, the A2 line, which can induce polyarthritis and can also be used to vaccinate rats against adjuvant arthritis. Although line A2 was selected for its proliferative response to mycobacteria, it also responded to collagen type II. To elucidate its role of responsiveness to collagen type II and the relationship between arthritogenicity and vaccination, we cloned A2 and selected a subline A2b. We now report that subline A2b, which bore a marker of helper/delayed hypersensitivity T lymphocytes, was strongly arthritogenic, but could not vaccinate against arthritis. Moreover, A2b showed no response to collagen type II. Therefore, reactivity to collagen type II is not a requisite for arthritogenicity, and mediation of arthritis and vaccination can be distinct properties of different populations of T lymphocytes. (7) and in humans with rheumatoid arthritis (8), it has been suggested that collagen type II may be a critical self-antigen in autoimmune arthritis (7).To investigate the pathogenesis of AA we developed lines of T lymphocytes from the draining lymph nodes of Lewis rats immunized to CFA (9). Line A2, selected because of its proliferative response to whole MT, could induce polyarthritis upon intravenous injection into irradiated Lewis rats. Cells of line A2 could also be used to vaccinate rats against subsequent attempts to induce AA by active immunization to CFA. We observed that in addition to responding strongly to MT, line A2 proliferated in vitro to a relatively slight but significant degree to collagen type II. Hence it was conceivable that some MT antigens might cross-react with self-collagen type II and that induction of arthritis and/or vaccination against AA might be the property of line cells reactive to collagen type II (9).The present experiments were done to test this hypothesis. Accordingly, we prepared a cloned subline, A2b, that was found to be more strongly arthritogenic than the parent A2 line. However, unlike the A2 line, the A2b subline could not induce resistance to AA. Moreover, subline A2b responded in vitro strongly to MT antigens but not at all to collagen type II. Thus, arthritogenicity and vaccination may be produced by separate populations of cells, and reactivity to collagen type II is not required to induce autoimmune arthritis. Finally, we were able to transfer arthritis with line cells that had been activated by the mitogen concanavalin A (Con A) in place of MT. This argues against the notion that disseminated MT antigens are the requisite target for AA and suggests that a target self-antigen exists in the joints. 211Line-mediated Arthritis in Rats J. Clin. Invest.

Adjuvant arthritis is an experimental disease of rats induced by immunization to antigens of Mycobacterium tuberculosis. Our observation that arthritis could be induced in irradiated rats by the A2 line of T lymphocytes in the absence of mycobacterial antigens suggested that adjuvant arthritis is an autoimmune disease. Moreover, the A2 line could be used to vaccinate unirradiated rats against the subsequent induction of adjuvant arthritis by active immunization to Mycobacteia. In the present study we found that thymus cells obtained from A2 vaccinated rats could transfer resistance to adjuvant arthritis to naive rats. This indicates that the mechanism of resistance induced by A2 vaccination is probably immunological and involves thymus-derived lymphocytes.