Renal transplantation in the inbred rat. 3. A study of heterologous anti-thymocyte sera.

Heterologous rabbit anti-rat thymocyte sera, its immunoglobulin G fraction, and the bivalent and univalent antibody fragments obtained by pepsin digestion are potent immunosuppressive reagents when tested in a system of renal allotransplantation between the LBN F(1) hybrid and Lewis rat strains. The AT F(ab')(2) is not lymphocytotoxic in vitro but has agglutinating ability, while the AT Fab' neither agglutinates nor is cytotoxic to rat lymphocytes, but will inhibit the in vitro reaction. The AT IgG and the F(ab')(2) are more immunogenic in their host than normal rabbit IgG and F(ab')(2), probably due to increased delivery of the antibody to the immune system. Donor pretreatment studies demonstrate that a cross-reacting, highly immunogenic antibody with anti-lymphocyte specificity may bind to renal sites and be transferred to the new host after transplantation. In addition, the crude unabsorbed anti-thymocyte antisera may induce a nephritis characteristic of immune complex disease which can be eliminated by complete absorption with serum proteins. Further in vivo and in vitro evidence is presented that the AT IgG contains small amounts of antibody to glomerular basement membrane antigens and may induce an autologous phase-nephrotoxic nephritis. The amount of in vivo binding by AT IgG to GBM was reduced by subcutaneous rather than intravenous administration. Most of the rabbit antisera tested contain antibody in low titer to sheep erythrocytes and in vivo experiments indicate that the nature of the immunodepressive effect of AT globulin to sheep erythrocytes is due in part to the passive transfer of antibody and is not necessarily due to a specific anti-lymphocyte effect.