The local graft versus host reaction in the rat as a tool for drug mechanism studies

Abstract

1. A local graft versus host reaction in rats permits the evaluation of drug action on (i) donor (parental) animals and (ii) recipient animals (F(1) hybrid) prior to establishing a lymphoid cell graft to detect drugs which might attenuate immunocompetence over a prolonged period (e.g. steroids).2. Treatment of the recipient animals after a lymphoid graft readily detects anti-proliferative agents and may disclose other agents which interfere with the recognition of non-self by viable graft cells.3. Treatment of the cell graft in vitro before innoculation into the recipient animal permits the detection of alkylating agents, which effectively deactivate graft cells at non-toxic concentrations.4. Examples are given of how this reaction may be used to evaluate functionally the effects of chemical modification of the cell surfaces of lymphocytes and to detect active metabolites generated from a precursor drug (e.g. cyclophosphamide).5. Some novel immunosuppressant drugs are described.