A Comparison of Thymectomized and Antithymocyte Serum-Treated Mice in Their Development of Hypersensitivity to Protein Antigens

Summary Mice of CF 1 strain thymectomized at birth were compared with similar mice which had been sham-operated, treated with normal rabbit serum, or treated with rabbit antiserum to mouse thymus for various time intervals after birth, with respect to ability to develop immediate and delayed hypersensitivity to ovalbumin and bovine serum albumin, and delayed hypersensitivity to tuberculoprotein. Hematologic and histologic changes in these various mice also were evaluated. Mice treated with antiserum or thymectomized at birth either failed to develop hypersensitivities to antigens injected early in the experiment, or they developed these hypersensitivities with slower than normal tempo. Suppression of hypersensitization in antiserum-treated animals was proportional to the length of time over which they were treated with this antiserum. Neither thymectomy nor antiserum treatments interfered with development of anamnestic responsiveness to these initially injected antigens, nor was the immunosuppressive effect more than temporary; thymectomized and treated animals responded normally, developing immediate and delayed hypersensitivities to bovine serum albumin when this was injected into them at the end of the experiment 6 months after thymectomy and approximately 4 months after the last antiserum treatment. None of the animals developed wasting disease. Single or multiple treatments with antiserum to mouse thymocytes caused peripheral lymphocyte counts to drop significantly while numbers of tissue plasma cells and peripheral large lymphocytes remained normal. In vitro examination of the properties of this antiserum revealed that although it would fix complement in the presence of thymus antigens it did not cause thymocyte agglutination or lysis. In long-term treated mice there were, in addition to depressed peripheral lymphocyte counts, histologic changes consisting of decreased lymphoid mass and loss of splenic germinal centers. But thymus glands in these animals remained anatomically intact. Hence, immunosuppression effected by anti-thymus antiserum treatments may be viewed either as due to lymphocyte suppression or as evidence supporting recent reports that a humoral thymic factor may control immunocompetence. If the latter alternative proves true, then rabbit anti-mouse thymus antiserum may contain antibody to this humoral factor which neutralizes its biologic effects.