Autoimmunity induced by type II collagen-coupled spleen cells.

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.