title: A comprehensive and quantitative analysis of the major specificities in rabbit antithymocyte globulin preparations.
abstract: Antithymocyte globulin (ATG) preparations are used for treatment and prevention of graft rejection episodes, graft versus host disease and aplastic anemia. The immunomodulatory and immuosuppressive properties of ATGs are mediated by their interaction with a large variety of antigens expressed on immune and nonimmune cell populations. We have conducted a comprehensive analysis on antibody specificities contained in rabbit ATGs in clinical use, ATG-Fresenius (ATG-F) and Thymoglobulin (THG). We have used retroviral expression cloning to identify novel ATG antigens and demonstrate that together with ATG antigens described earlier, these molecules account for the majority of ATG antibodies directed to human cells. Moreover, we have employed cell lines engineered to express antigens at high levels to quantify the antibodies directed to each ATG antigen. We have used cell lines expressing the T cell receptor complex, CD2 and CD28 to remove antibodies to these antigens from ATG preparations and demonstrate that this treatment abrogated the ability of ATGs to induce activation and forkhead box P3 expression in T cells. Comprehensive information and differences on the antigens targeted by ATG-F and THG as well as novel approaches to assess their functional properties are the basis for a better understanding of their immunomodulatory capacities and might eventually translate into improved ATG-based regimen.
authors.affiliation: Division of Immune Receptors and T Cell Activation, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Popow
authors.forename: J
authors.initials: J
authors.lastname: Leitner
authors.forename: K
authors.initials: K
authors.lastname: Grabmeier-Pfistershammer
authors.forename: O
authors.initials: O
authors.lastname: Majdic
authors.forename: G-J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: M
authors.initials: M
authors.lastname: Kundi
authors.forename: P
authors.initials: P
authors.lastname: Steinberger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000737:chemistry*; D018801:CD2 Antigens / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015723:Gene Library; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000737:chemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D018801:CD2 Antigens; D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; C512542:thymoglobulin
keywords: Antibodies; FOXP3; antithymocyte globulins; expression cloning; immunosuppression; specificities