The oral administration of 3 μg but not 300 μg of type II collagen (CII) significantly suppressed adjuvant arthritis in rats that was induced by immunization with Mycobacterium tuberculosis. Feeding 5000 units of type I interferon was also effective in downregulating the disease. More suppression of adjuvant arthritis was observed when both CII and interferon were orally given. Delayed-type hypersensitivity responses to M. tuberculosis were inhibited in interferon-but not in CII-fed animals. There were no delayed responses to CII in M. tuberculosis-immunized rats fed either CII or interferon. However, the delayed response to M. tuberculosis plus CII was significantly reduced by CII as well as interferon given orally. Feeding both CII and interferon was more effective in suppressing the delayed responses to M. tuberculosis plus CII. A similar suppression was observed in proliferative responses of lymph-node cells to M. tuberculosis, CII, or M. tuberculosis plus CII in-vitro.
These results suggest that the suppression of adjuvant arthritis by oral administration of CII is due to tolerance to CII in which a bystander suppression mechanism appears to be involved. Orally administered interferon seems to suppress nonspecifically cellular immune responses. The oral administration of CII in combination with interferon may be a novel way to treat T cell-mediated diseases.