Toward an Understanding of the Mechanisms of Classical Conditioning of Antibody Responses

Abstract

Mice of different ages were subjected to repeated exposure to cyclophosphamide:saccharin (conditioned), or cyclophosphamide:saccharin followed by saccharin only (extinguished). Only young animals in the former group showed a decreased IgG antibody-forming-cell (AFC) response after challenge with sheep erythrocytes (SRBC) in the presence of saccharin. When irradiated conditioned young animals were used as recipients of antigen-challenged spleen cells from nonconditioned mice they were found to support a greater immune response than nonconditioned recipients. Similarly, cells from conditioned young mice gave a greater immune response in naive recipients than did cells from nonconditioned mice. Only when cells from conditioned young mice rather than conditioned "aged" mice were studied in irradiated conditioned young recipients was immunosuppression observed. These data are most consistent with a specific host cell:environment interaction being responsible for the conditioned immunosuppression observed in young mice. A deficit in both cells/environment apparently occurs during aging. At least one of these deficiencies seems related to loss of a suppressor T-cell population with age in conditioned mice.