Behaviorally conditioned suppression of murine T-cell dependent but not T-cell independent antibody responses

The aversive and immunosuppressive effects of cyclophosphamide (CY, 250 mg/kg IP), an unconditioned stimulus (UCS), were paired with the presentation of a novel saccharine flavored drinking solution (SAC), a conditioned stimulus (CS), in female Balb/c mice. The objective was to determine the temporal relationship between presentation of the CS (SAC) and immunization with sheep red blood cell (SRBCs), a T-cell dependent antigen, and type III pneumococcal polysaccharide (S3), a T-cell independent antigen, on subsequent antibody responses. Reexposure to the CS or UCS occurred on days -4, -2, 0, +2, or +4 relative to immunization. Primary antibody responses in each group were measured six days following immunization. A strong association between the CS and the UCS developed, producing flavor aversions as evidenced by decreased SAC consumption. CY administration by itself consistently suppressed both types of antibody responses. CS presentation (i.e., SAC) had no significant effect on anti-S3 antibody response. However, the anti-SRBC response was significantly depressed following CS exposure. Exposure to the CS only on days -4 or +2 relative to immunization resulted in statistically significant suppression of antibody response to SRBC's while exposure on days -2, 0, and +4 resulted in anti-SRBC antibody suppression that did not reach significance. These results support the hypothesis that conditioning of antibody responses is relatively specific for T-cell dependent antigens, and that the timing of CS presentation relative to immunization is important in conditioning a suppression of antibody responses.