title: FoxP3+, and not CD25+, T cells increase post-transplant in islet allotransplant recipients following anti-CD25+ rATG immunotherapy.
abstract: Anti-CD25 antibodies are used as an induction therapy in islet allotransplantation for type 1 diabetes. Although previous reports suggested that anti-CD25 treatment may lead to depletion of CD4+CD25+ regulatory T cells (Tregs) and questioned its use in tolerance-promoting protocols for transplantation, the effect of anti-CD25 antibodies on the frequency and function of Tregs remains unclear. We examined the effect of anti-CD25 antibody, daclizumab, in vivo on Tregs in islet allograft recipients enrolled in a single-center study and monitored post-transplant. Our data shows that the reduction in CD25+ Treg cells observed post-transplant is due to masking of CD25 receptor by daclizumab and not due to depletion. In addition, using Treg marker, FoxP3, we show that anti-CD25+ ATG treatment leads to an increase in FoxP3+ Tregs post-transplant. These data suggest that anti-CD25-based therapy has beneficial effects on Tregs and combined with ATG may be a promising therapy for autoimmunity and transplantation.
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hire
authors.forename: Diem K
authors.initials: DK
authors.lastname: Ngo
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Stewart-Maynard
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hering
authors.forename: Pratima
authors.initials: P
authors.lastname: Bansal-Pakala
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000276:immunology / Q000627:therapeutic use*; D001323:Autoantibodies / Q000627:therapeutic use*; D049109:Cell Proliferation; D000077561:Daclizumab; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D007167:Immunotherapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D018655:Lymphocyte Count; D011956:Receptors, Cell Surface / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D001323:Autoantibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D011956:Receptors, Cell Surface; C006606:anti-thyroglobulin; D000077561:Daclizumab; C512542:thymoglobulin