Local administration of cytostatic drugs enhances delayed-type hypersensitivity to Sendai virus in mice

Cytostatic drugs known to exert immunomodulatory activity were studied in a local treatment protocol as to their effect on development of cell-mediated immunity to Sendai virus in mice. Strong enhancement of delayed-type hypersensitivity (DTH) was observed after treatment with the active cyclophosphamide (CY) derivative Z 7557 or the plant alkaloid VP-16 at the site of sensitization. Optimal enhancement of DTH was obtained after priming with subimmunogenic doses of Sendai virus and treatment with low, virtually nontoxic drug doses. Immunoenhancement is ascribed to elimination of CY-sensitive suppressor cells from the draining lymph nodes. The relevance of our findings with respect to protective immunity is discussed.