Tolerogenic activity of polymerized type II collagen in preventing collagen-induced arthritis in rats

Rats were exposed parenterally or pergastrically to polymerized type II collagen (POLCII) and became resistant to the subsequent induction of disease with arthritogenic type II collagen (CII) administered intradermally in Freund's incomplete adjuvant (FIA). POLCII was prepared by cross-linking native soluble arthritogenic CII, from bovine nasal septal cartilage, with glutaraldehyde. POLCII injected intradermally in FIA did not induce arthritis. Animals treated in this manner were resistant for a period of at least 100 days to induced disease. The change in the properties of the CII from an arthritogen to a tolerogen was related to the amount of glutaraldehyde (used to polymerize the CII) which was assumed to control the extent of cross-linking of the CII. Highly cross-linked POLCII administered pergastrically, like soluble CII, was not arthritogenic but was tolerogenic, inducing a state of unresponsiveness to a challenge with arthritogenic CII. In general serum anti-CII antibody levels were higher in arthritic than in tolerized non-arthritic rats. It is concluded that the breaking of self-tolerance to CII depends upon its physical state. When polymerized and insoluble, a form analogous to that in which it exists naturally, it is tolerogenic.