title: Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin.
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
authors.affiliation: Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Maja
authors.initials: M
authors.lastname: Buszko
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Center of Operative M edicine, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Benno
authors.initials: B
authors.lastname: Cardini
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Center of Operative M edicine, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Oberhuber
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Center of Operative M edicine, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Oberhuber
authors.affiliation: Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Bojana
authors.initials: B
authors.lastname: Jakic
authors.affiliation: Central Laboratory Animal Facility, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Anja
authors.initials: A
authors.lastname: Beierfuss
authors.affiliation: Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Wick
authors.affiliation: Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cappellano
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009928:Organ Specificity; D011817:Rabbits; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D017252:CD3 Complex; C115335:CD3E protein, human; D007166:Immunosuppressive Agents