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Treatment of rats with intravenous injection of 1 mg of soluble native type II collagen induced resistance against the subsequent induction of active arthritis by type II collagen immunization. This resistant state was accompanied by suppressed antibody response and delayed-type hypersensitivity (DTH) skin reaction to type II collagen. However, pretreatment of rats with 20 mg/kg of cyclophosphamide (CY), an agent reputed to damage suppressor T-cell function, 2 days before intravenous injection of soluble type II collagen abrogated the antigen-induced resistance against the subsequent induction of active arthritis. The DTH skin reaction to type II collagen was completely restored and the antibody response to type II collagen was significantly though not completely restored by CY pretreatment. These results provide evidence that antigen-induced resistance to collagen arthritis is mediated, at least in part, under the control of CY-sensitive events.
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