Old and New Strategies in the Conditioning of Immune Responses

Classical (Pavlovian) conditioning of immune responses was demonstrated by Metal'nikov and his colleagues at the Pasteur Institute in Paris during the 1920s. These experiments, although controversial, were repeated and extended, largely in the Soviet Union, by Dolin, Krylov, Flerov, Luk'yanenko and many others during the 1950s and '60s. Both immunosuppression and immunoenhancement were reported, with many antigens and in several species including man. After a long hiatus, new interest in this subject was revived in the United States, starting with the work of Ader and Cohen on one-trial association learning leading to immunosuppression, and extending again to a new wave of reports from the United States, Canada, Germany and other countries on both conditioned suppression and conditioned enhancement of several host-defense systems, including natural killer cell activity. It already has been demonstrated that conditioning in mice can slow down the growth of tumors and, in some instances, even completely reverse tumor growth. This work is briefly discussed, with emphasis on some of the more recent findings. Applications to human subjects are suggested. The doors are just being opened: the possibilities for new research, for new discoveries, and for new clinical applications are endless.