Key points are not available for this paper at this time.
Abstract Reactivity to self was induced by injecting rats subcutaneously (s.c.) with spleen cells coupled to native homologous or heterologous type II collagens. Native homologous types I and III collagens, as well as denatured type II collagen, were nonimmunogenic in this system. Cellular sensitization to type II collagen was detected by radiometric ear, 3H-thymidine incorporation, and leukocyte inhibitory factor (LIF) assays. Sensitization was antigen specific and was produced using either syngeneic Lewis (Lew) or histoincompatible Wistar-Lewis (W-L) and Sprague-Dawley (S-D) spleen cells. These injections did not induce a humoral response, even in W-L and S-D rats boosted at weekly intervals. In contrast, hemagglutinating antibodies to type II collagen developed in W-L rats pretreated with a low dose of cyclophosphamide before injection of collagen-coupled cells. Antibodies were also produced without cyclophosphamide by injecting Brown-Norway (B-N) rats with allogeneic cells coupled to collagen. W-L rats injected with type II collagen-coupled cells in incomplete Freund’s adjuvant (ICFA) developed arthritis, but no disease was observed in the rats sensitized by collagen-coupled cells without ICFA or in W-L rats injected with collagen-coupled cells and ICFA in separate sites. W-L rats injected with collagen-coupled cells and administered immunoglobulin from arthritic donors i.v. still failed to exhibit arthritis. These studies suggest that autoimmunity can result from the interaction of a host constituent with spleen cell membrane determinants, that native type II collagen functions as an exceptional autoimmunogen in this system, and that 1 or more effector mechanisms requisite for the induction of arthritis is not primed by the injection of collagen-coupled cells in the absence of ICFA.
Schoen et al. (Tue,) studied this question.