Immunity to homologous collagens and cartilage proteoglycans in rabbits.

The in vitro incorporation of [3H]-thymidine into spleen cells was used to show that rabbits with experimentally-induced inflammatory arthritis of 1-4 months duration often develop cellular immunity to purified homologous cartilage proteoglycans, type I and III collagens and, less frequently, to type II collagen. Responses to collagens were primarily directed to antigenic determinants exposed on peptides in degraded molecules, whereas responses to proteoglycans were seen with both native and degraded molecules. These in vitro blastogenic responses were shown to be completely dependent on the presence of T lymphocytes in the cultures. This expression of immunity was not demonstrable in rabbits with long duration arthritis (7-12 months) with any of the antigens tested. Some rabbits injected with homologous proteoglycans demonstrated T-cell-dependent cellular, but not humoral, immunity to the injected antigens. In contrast, rabbits injected with heterologous human proteoglycans developed cellular and humoral immunity to the immunizing proteoglycan, but failed to develop cellular immunity to rabbit proteoglycan. Some of these rabbits did, however, produce circulating antibodies which reacted with rabbit proteoglycans. Moreover, antibodies produced by immunizing rabbits with proteoglycans from bovine, chicken and rat cartilages and the hyaluronic acid binding region from rat cartilage proteoglycan often cross-reacted with rabbit proteoglycan, indicating that there are species-common antigenic determinants present in these proteoglycans and in the hyaluronic acid binding region and that these are recognizable in rabbit proteoglycans by rabbit antibodies. This ability to induce selectively cellular or humoral immunity to proteoglycans should be useful for future investigations of the role of such immunity in the pathogenesis of arthritis, although induction of immunity to proteoglycan was not accompanied by any demonstrable synovitis in these rabbits as has been observed in some strains of rats and mice for type II collagen.