title: Depletion of alloreactive T-cells in vitro using the proteasome inhibitor bortezomib preserves the immune response against pathogens.
abstract: Current graft-versus-host disease (GVHD) inhibition approaches lead to abrogation of pathogen-specific T-cell responses. We propose an approach to inhibit GVHD without hampering immunity against pathogens: in vitro depletion of alloreactive T cells with the preoteasome inhibitor bortezomib. We show that PBMCs stimulated with allogeneic cells and treated with bortezomib greatly reduce their ability to produce IFN-γ when re-stimulated with the same allogeneic cells, but mainly preserve their ability to respond to citomegalovirus stimulation. Unlike in vivo administration of immunosuppressive drugs or other strategies of allodepletion, in vitro allodepletion with bortezomib maintains pathogen-specific T cells, representing a promising alternative for GVHD prophylaxis.
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca and Centro de Investigación del Cáncer/IBMCC (CIC/CSIC) Salamanca, Spain. belen_blancod@yahoo.es
authors.forename: Belén
authors.initials: B
authors.lastname: Blanco
authors.forename: Luis Ignacio
authors.initials: LI
authors.lastname: Sánchez-Abarca
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero-Velázquez
authors.forename: Carlos
authors.initials: C
authors.lastname: Santamaría
authors.forename: Susana
authors.initials: S
authors.lastname: Inogés
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Pérez-Simón
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D007371:Interferon-gamma