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Dichotomy and Improved Specificity of Immunosuppressive Effect of Anti-Thymocyte Globulin¹

From the Division of Experimental Biology, Baylor College of Medicine, Houston, Texas 77025

Abstract

Cytotoxicity of horse anti-mouse thymocyte globulin (HAMTG) against mouse thymus was completely removed by multiple absorptions with mouse thymus but not by absorptions with kidney or spleen. Cytotoxicity against spleen was completely removed by multiple absorption with spleen but not by absorption with kidney or thymus. Absorptions with thymus resulted in complete removal of immunosuppressive potency as judged by duration of survival of H-2 incompatible murine cardiac allografts, but absorptions with kidney or spleen did not significantly affect the capacity to prolong cardiac allograft survival. HAMTG treatment significantly reduced hemolytic plaque-forming cells (PFC), rosette-forming cells (RFC) and hemagglutinating antibody (HA) titers in mice immunized with sheep red blood cells (SRBC). Absorptions with either spleen or thymus, but not kidney, removed this immuno-suppressive activity against PFC, RFC and HA. These studies suggest that HAMTG, in addition to containing antibodies specific for thymus, also contains antibodies which are cross-reactive with spleen and kidney. The thymus specific antibodies are of major importance in determining the ability to promote cardiac allograft survival. Antibodies either specific for or cross-reactive between thymus and spleen are important for suppression of the spleen dependent PFC, RFC and HA response to SRBC. The fact that exhaustive absorption of HAMTG with spleen completely removed the ability to suppress PFC, RFC and HA without reducing the ability to suppress allograft rejection suggests that a different population of "T" cells is necessary for allograft rejection than for humoral antibody formation.

Footnotes

¹ This work was supported by United States Public Health Service Grants HE-05435, CA-12093 and K6-CA-14, 219.