Characterization of the delayed hypersensitivity response to a protein antigen in the mouse--I. Kinetics of reactivity and sensitivity to classical immunosuppressants.

Several parameters of the delayed hypersensitivity response (DHR) to a protein antigen, keyhole limpet hemocyanin (KLH), were investigated. Female B6C3F1 mice were sensitized with KLH suspended in either complete Freund's Adjuvant (CFA) or sterile saline. When the mice were sensitized twice, the magnitudes of these responses were equivalent as measured by a radioisotopic procedure reflecting the influx of monocytes. With only a single sensitization, there was a 37% decrease in the response of CFA-treated mice and a dramatic (82%) decrease in the response of saline-treated mice. Utilizing two sensitizing injections in male CD-1 mice, the kinetics of the responses were determined to be equivalent regardless of whether KLH was suspended in CFA or saline in that both responses were persistent for up to 5 weeks between the second sensitization and challenge. Ear thickness in CFA-treated mice was twice that of the saline-treated mice at 1, 3 and 5 weeks. This increased swelling was not due to an increase in the vascular permeability as measured by the extravasation of a radiolabelled protein. There was a marked increase in the total area of fibrin in both sensitized groups when compared to unsensitized mice; but no difference between the groups. The sensitivity of these responses to immunosuppressants was determined in male CD-1 mice exposed subchronically (14 day) to dexamethasone (DEX) and cytoxan (CTX). There was a marked increase in the suppression by DEX in mice sensitized to KLH in saline as compared to mice sensitized to KLH in CFA. In contrast, the sensitivity to suppression by cyclophosphamide was not affected by the presence of CFA.