Abstract
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Ɛ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points. We found a significant T cell depletion in this mouse model. In addition, regulatory T cells (Tregs) proved to be less sensitive to depletion than the rest of T cells and the Treg:non-Treg ratio was therefore increased. Finally, we also investigated the effect of ATG in a heterotopic allogenic murine model of heart transplantation. Survival and transplant function were significantly prolonged in ATG-treated mice. In conclusion, we showed (a) an immunosuppressive effect of ATG in this humanized mouse model which is exclusively mediated by reactivity against human CD3Ɛ; (b) provided evidence for a relative resistance of Tregs against this regimen; and (c) demonstrated the immunomodulatory effect of ATG under these experimental circumstances by prolongation of heart allograft survival.
Highlights
Thymoglobulin (ATG) is a solution of rabbit anti-human thymocytes immunoglobulin
We found that a single intravenous (i.v.) injection of ATG into BALB/c huCD3Ɛ transgenic mice resulted in T cell depletion in the circulation and in the secondary lymphoid organs, with concomitant preservation of Tregs
By staining with anti-mouse and anti-huCD3Ɛ monoclonal antibodies (mAbs) we showed that there was a complete loss of huCD3Ɛ receptor staining after incubation with ATG as compared to control Ig
Summary
Thymoglobulin (ATG) is a solution of rabbit anti-human thymocytes immunoglobulin. It has been used as an immunosuppressive agent in the prevention and treatment of transplant rejection such as kidney, liver and heart for decades [1,2]. The immunosuppressive effects of ATG are based on complement-mediated cell lysis and apoptosis [3]. ATG depletes T cells in CD3ε humanized mice
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