The structural basis of cell-mediated immunological reactions of collagen. Characteristics of cutaneous delayed hypersensitivity reactions in specifically sensitized guinea-pigs.

Cell-mediated immunological properties of collagen were studied in guinea-pigs employing cutaneous delayed hypersensitivity reactions. The animals were sensitized by a single injection of highly purified native collagen in Freund's complete adjuvant (FCA). Reactivity could be induced with 150 μg of calf collagen. Maximal reactivity was obtained 20 days after sensitization and persisted for more than 3 months. Histologically, the reactions displayed the typical features of delayed reactions with infiltration of predominantly mononuclear cells. No reactivity was induced in animals injected with FCA alone, with collagen in Freund's incomplete adjuvant (FIA), or with guinea-pig collagen in Freund's complete adjuvant. Reactivity was impaired when carrageenan was injected intraperitoneally at the time of challenge. Cyanogen bromide digested collagen was still reactive in sensitization as well as in elicitation. The reaction was found to be species specific in the sense that maximal reactions were obtained when the challenging collagen was from the same species as the sensitizing preparation. In vitro, denatured rat collagen was found to inhibit the migration of macrophages from specifically sensitized animals. By alterations of the immunization schedule antibodies, reactive with collagen in a haemagglutination system, could be induced. The system lends itself to a comparative investigation of the structural requirements on a natural protein for the induction of the cell-mediated and the humoral immune response.