Immunoregulatory, especially immunosuppressive regimens are strategies used as treatments in transplantation and autoimmune diseases. Since lymphocytes are the most important players in mounting immune responses, lymphodepleting agents are investigated and developed for clinical use as immunosuppressive treatments. This thesis describes efforts to elucidate the effects and mechanisms of action of polyclonal and monoclonal anti-T cell antibodies in the context of transplantation and autoimmune diseases. Polyclonal rabbit anti-human thymocyte globulin (ATG) is a T cell depleting agent used since decades as induction therapy in solid organ and stem cell transplantation. It is produced by immunizing rabbit with human thymocytes. ATG has been studied, both in animal models as well as in vivo and in vitro in humans and was shown to cause rapid and profound T cell depletion. However, due to its polyclonal character, ATG also affects other cells of lymphoid and non-lymphoid origin as it binds not only antigens found on T cells. Data presented in this thesis show that anti-human ATG can be studied in transgenic mice expressing the human CD3 receptor, i.e., a part of the T cell receptor (TCR). By using the above-mentioned animal model, we show that under these circumstances the effect of ATG is exclusively mediated by binding to the human CD3 receptor. We find that one single, low dose of ATG depletes T cells in the circulation but also in secondary lymphoid organs. Interestingly, regulatory T cells are less sensitive to ATG mediated T cell depletion then the rest of T cells, which results in increased ratio of regulatory to non-regulatory T cells. Moreover, ATG prolongs graft survival in a heterotopic cervical heart allotransplantation model. In addition, the immunomodulatory effect of ATG was investigated in vitro using human peripheral blood mononuclear cells (PBMCs). In vitro stimulation with ATG results in an upregulation of Foxp3 in CD4 cells and in suppressive activity, Immunoregulatory, especially immunosuppressive regimens are strategies used as treatments in transplantation and autoimmune diseases. Since lymphocytes are the most important players in mounting immune responses, lymphodepleting agents are investigated and developed for clinical use as immunosuppressive treatments. This thesis describes efforts to elucidate the effects and mechanisms of action of polyclonal and monoclonal anti-T cell antibodies in the context of transplantation and autoimmune diseases. Polyclonal rabbit anti-human thymocyte globulin (ATG) is a T cell depleting agent used since decades as induction therapy in solid organ and stem cell transplantation. It is produced by immunizing rabbit with human thymocytes. ATG has been studied, both in animal models as well as in vivo and in vitro in humans and was shown to cause rapid and profound T cell depletion. However, due to its polyclonal character, ATG also affects other cells of lymphoid and non-lymphoid origin as it binds not only antigens found on T cells. Data presented in this thesis show that anti-human ATG can be studied in transgenic mice expressing the human CD3 receptor, i.e., a part of the T cell receptor (TCR). By using the above-mentioned animal model, we show that under these circumstances the effect of ATG is exclusively mediated by binding to the human CD3 receptor. We find that one single, low dose of ATG depletes T cells in the circulation but also in secondary lymphoid organs. Interestingly, regulatory T cells are less sensitive to ATG mediated T cell depletion then the rest of T cells, which results in increased ratio of regulatory to non-regulatory T cells. Moreover, ATG prolongs graft survival in a heterotopic cervical heart allotransplantation model. In addition, the immunomodulatory effect of ATG was, Maja Buszko, M.Sc., Kumulative Dissertation aus vier Artikeln, Medical University Innsbruck, Dissertation, 2016, OeBB, (VLID)1542487