Effects of conjugated and nonconjugated antithymocyte globulin and trenimon on T lymphocytes and skin graft rejection.

These studies were undertaken to investigate the use of a technique for "homing" of an alkylating agent to lymphocytes as an immunosuppressive approach to inhibit allograft rejection. Trenimon (Tr) was bound covalently to antithymocyte globulin (ATG) and the effects of the complex on peripheral blood cells, thymus cells, spleen cells, and on foreign skin graft rejection assessed. When rabbit ATG was bound covalently to Tr, an alkylating agent, the conjugate (ATG-Tr) retained both complement-dependent antithymus cell acitivity and alkylating activity in vitro, but these activities were reduced. In vivo ATG decreased lymphocytes and increased neutrophils in the blood. ATG-Tr reduced circulating lymphocytes to lower levels and partially attenuated the rise in neutrophils. The in vivo effects of ATG, Tr, ATG-Tr, and ATG mixed with Tr (ATG + Tr) on thymus cells, spleen cells, T lymphocytes in the spleen, and rejection of a foreign skin graft were compared. Tr decreased all cell types, especially thymocytes, but did not delay graft rejection. ATG and ATG-Tr decreased thymocytes, eradicated T cells from the spleen, and delayed graft rejection 3-fold. ATG + Tr decreased thymocytes as Tr had done, eradicated T cells from the spleen, and delayed graft rejection 5-fold. It was concluded that ATG-Tr possessed antithymocyte antibody activity and Tr alkylating activity, but did not confer an immunological advantage over ATG alone, and that ATG and Tr mixed together unbound acted synergistically to delay graft rejection.