| Abstrakt: |
Twenty horse antihuman lymphocyte sera or globulins were tested in vivo for their immunosuppressive and toxic effects in monkeys and chimpanzees. Prolongation of skin allograft survival was the main parameter to assess immunosuppression. About one-third of the agents were moderately to highly effective; the others had an unacceptably low therapeutic index. Chimpanzees, known to share HL-A leukocyte antigens with man, seemed, as in previous experiments, more susceptible to the immunosuppression but also to the toxic properties of antihuman sera. The predictive value of this “primate assay” for clinical application of the agents has not been strictly proven; however, there are reasons to believe that a certain value can be attached to the results of the test, particularly to the results obtained in chimpanzees. On the basis of this assumption, data obtained so far indicate that it is difficult to produce effective horse antihuman sera using spleen cells as antigen; on the other hand, four antithoracic duct cell sera (two prepared with adjuvant, two without) were among the most effective agents tested so far. Horses immunized with thymocytes or blood lymphocytes (three sera of each type) gave variable results. The relatively small number of sera and the many variables involved do not yet permit, firmer conclusions, primarily because results of standardized clinical trials, the most stringent criteria to assess the reliability of the primate assay, are not yel available for any of the agents tested. In view of the importance of establishing in vitro test systems capable of predicting in vivo characteristies of antihuman lymphocyte sera, the majority of the agents described in the present paper were submitted to one of the two in vitro assays known to have such predictive value in rodents. The results are reported elsewhere by J. F. Bach et al. (3). |
