Behaviorally conditioned enhancement of delayed-type hypersensitivity in the mouse

Cyclophosphamide (CY), previously used to condition suppression of a number of different immune responses, was used to condition an enhancement of a delayed-type hypersensitivity (DTH) response in mice. Three weeks before sensitization with sheep red blood cells (SRBC), mice were conditioned by pairing their consumption of a saccharin solution (SAC) with injection of CY. Two, three, and four days after sensitization (Day 0), animals were reexposed to SAC and, on Day +3, they were injected with a low dose of CY. This dose suppressed the DTH response to a challenge with SRBC on Day +4 in both conditioned and control animals. Following rechallenge with SRBC on Days +11 and +18, however, DTH responses were enhanced. Conditioned mice that had been reexposed to SAC showed a significantly greater enhancement than either nonconditioned animals or conditioned mice that were not reexposed to SAC. Thus, enhancement as well as suppression of immune responses can be conditioned with CY.