title: The effect of rabbit antithymocyte globulin on human mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) possess immunomodulatory properties which are of key interest for their application in autoimmunity and transplantation. In transplantation, administration of MSCs has shown promising results in preclinical models and has recently moved to clinical trials. Therefore, it is important to study the interactions between MSCs and immunosuppressive drugs currently used in transplantation. We aimed to analyze the effect of rabbit antithymocyte globulin (rATG) MSCs. MSCs were obtained from perirenal fat of kidney donors and exposed to ranging doses of rATG (Thymoglobulin(®) , Genzyme; 0.5-100 μg/ml). Binding of rATG, effects on viability and susceptibility to be killed by cytotoxic lymphocytes as well as effects on their immunosuppressive potential of MSCs were tested. rATG binds dose-dependently to MSCs. This binding was associated with slightly impaired viability after 48 and 72 h when compared with nonexposed MSCs. In contrast to nontreated MSCs, rATG preexposed MSCs were susceptible to be lysed by cytokine-activated CD8(+) cytotoxic cells and NKT cells. The capacity of MSCs to suppress the proliferation of anti-CD3/CD28 activated CD4 and CD8 T cells were reduced by the presence of rATG in the culture. rATG reduces the viability and antiproliferative capacity of MSCs in a dose-dependent manner and converts them into targets for CD8 T cells and NKT cell lysis.
authors.affiliation: Transplantation Laboratory, Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. m.franquesa@erasmusmc.nl
authors.forename: Marcella
authors.initials: M
authors.lastname: Franquesa
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Sander S
authors.initials: SS
authors.lastname: Korevaar
authors.forename: Anja U
authors.initials: AU
authors.lastname: Engela
authors.forename: Marieke
authors.initials: M
authors.lastname: Roemeling-van Rhijn
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyo
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000378:metabolism / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011817:Rabbits
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents