title: Lymphodepletive effects of rabbit anti-pig thymocyte globulin in neonatal swines.
abstract: Lymphodepletive agents play important role in different clinical applications or experimental transplant studies. In order to facilitate preclinical pediatric transplant studies, we have developed the rabbit anti-pig thymocyte globulin (pATG) and studied its effects in neonatal swines. In vitro assays showed that pATG can bind to lymphocytes and neutrophils in a dose-dependent manner and lyse peripheral blood mononuclear cells by apoptosis and complement-dependent cytotoxicity. In vivo, pATG as a monotherapy was administered at different doses (2.5, 5, 20, 40 and 80mg/kg) in newborn pigs. Results showed that pATG induced a dose-dependent but transient T-cell depletion in peripheral blood. Lymphodepletion was also observed in lymph nodes, spleen and thymus. Pharmacokinetic studies showed dose-related cell-bound pATG on lymphocytes, as well as the presence of free pATG in the serum. Both cell-bound and free pATG levels decreased gradually after administration. Interestingly, adjuvant mycophenolate mofetil (MMF) given at 1g/m2/day for 1week successfully maintained pATG-induced T-cell depletion. In conclusion, pATG administration can cause transient T-cell depletion in neonatal pigs and this effect can be maintained by MMF. Therefore, we have developed an original immunosuppressive regimen that can be used for transplantation studies in swine model.
authors: Université de Lyon, VetAgro Sup, Chair of Transplantation, Marcy l'Etoile, France; Plastic and Reconstructive Department, Xijing Hospital, Xi'an, China.
authors: Hua
authors: H
authors: Pan
authors: Université de Lyon, VetAgro Sup, Chair of Transplantation, Marcy l'Etoile, France; Hand Surgery Department, Clinique du Parc, Lyon, France.
authors: Aram
authors: A
authors: Gazarian
authors: HLA Laboratory, L'Etablissement Français du Sang Rhône-Alpes, Lyon, France.
authors: Isabelle
authors: I
authors: Mollet
authors: HLA Laboratory, L'Etablissement Français du Sang Rhône-Alpes, Lyon, France.
authors: Virginie
authors: V
authors: Mathias
authors: HLA Laboratory, L'Etablissement Français du Sang Rhône-Alpes, Lyon, France.
authors: Valérie
authors: V
authors: Dubois
authors: Department of Hematology, Centre Hospitalier Lyon-Sud, Pierre Benite, France.
authors: Mohamad
authors: M
authors: Sobh
authors: Université de Lyon, VetAgro Sup, UPSP ICE 2011-03-101 'Interactions Cellules Environnement', Veterinary Campus of Lyon, Marcy l'Etoile, France.
authors: Samuel
authors: S
authors: Buff
authors: Department of Transplantation, Hôpital Edouard Herriot, Lyon, France.
authors: Jean-Michel
authors: JM
authors: Dubernard
authors: Department of Hematology, Centre Hospitalier Lyon-Sud, Pierre Benite, France.
authors: Mauricette
authors: M
authors: Michallet
authors: Cancer Research Center Lyon (CRCL), UMR INSERM 1052 CNRS 5286, Centre Leon Berard, Lyon, France. Electronic address: marie-cecile.michallet@lyon.unicancer.fr.
authors: Marie-Cécile
authors: MC
authors: Michallet
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D000920:Antibody-Dependent Cell Cytotoxicity; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D017209:Apoptosis; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005240:Feasibility Studies; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology*; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000627:therapeutic use; D009504:Neutrophils / Q000276:immunology*; D011817:Rabbits; D013552:Swine
chemical_list: D000276:Adjuvants, Immunologic; D000961:Antilymphocyte Serum; D003165:Complement System Proteins; D009173:Mycophenolic Acid
keywords: Anti-thymocyte globulin; Neonates; Swines; T-cell depletion; Tolerance induction; Transplantation