Effect of antithymocyte globulin on histocompatibility antigen recognition in man

Nonmajor histocompatibility complex (non-MHC) antigens are important targets of graft rejection and graft-versus-host disease in clinical transplantation. Little is known regarding immunity to non-MHC antigens. To study this problem we evaluated the effect of antihuman thymocyte globulin (ATG) on reactivity in autologous and allogeneic mixed lymphocyte cultures and activity in a model of immunity to non-MHC antigens, the response to trinitrophenyl (TNP)-modified autologous cells. Primary proliferative responses to autologous B lymphocytes, allogeneic cells, and TNP-modified autologous cells were all inhibited by ATG treatment. Secondary proliferative responses and cytotoxicity to TNP-modified autologous cells were also inhibited as was cross-reactive cytotoxicity to TNP-modified allogeneic cells. These data indicate that both MHC-restricted and MHC-nonrestricted immune responses to modified self-antigens and possibly to non-MHC antigens are sensitive to ATG treatment. ATG may be useful in clinical situations where the objective of immunosuppression is to inhibit immunity to non-MHC antigens such as after HLA-matched kidney grafting or bone marrow transplantation.