title: Ex vivo-expanded CD4+CD25+ immunoregulatory T cells prevent graft-versus-host-disease by inhibiting activation/differentiation of pathogenic T cells.
abstract: CD4+CD25+ immunoregulatory T cells (Tregs) can be administered to inhibit graft-vs-host disease (GVHD) while preserving graft-vs-leukemia activity after allogeneic bone marrow transplantation in mice. Preclinical studies suggest that it is necessary to infuse as many Tregs as conventional donor T cells to achieve a clinical effect on GVHD. Thus, it would be necessary to expand Tregs ex vivo before transplantation. Two strategies have been proposed: expansion of Tregs stimulated by anti-CD3/CD28-coated microbeads for polyclonal activation or by host-type allogeneic APCs for selecting Tregs specific for host Ags. In this study, we describe the mechanisms by which ex vivo-expanded Tregs act on donor T cells to prevent GVHD in mice. We demonstrate that expanded Tregs strongly inhibited the division, expansion, and differentiation of donor T cells, with a more pronounced effect with Tregs specific for host Ags. These latter cells permit the efficient and durable control of GVHD and favor immune reconstitution.
authors.affiliation: Biologie et Thérapeutique des Pathologies Immunitaires, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Trenado
authors.forename: Muriel
authors.initials: M
authors.lastname: Sudres
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Tang
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grégoire
authors.forename: Mark
authors.initials: M
authors.lastname: Bonyhadi
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Benoît L
authors.initials: BL
authors.lastname: Salomon
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014019:Tissue Donors