title: In vivo activation of transferred regulatory T cells specific for third-party exogenous antigen controls GVH disease in mice.
abstract: Treg cells hold enormous promise for therapeutic application in GVH disease, a lethal complication of allogeneic HSC transplantation. Mouse studies showed that donor-derived recipient-specific Treg (rsTreg) cells are far more efficient than polyclonal Treg cells in suppressing GVH disease. However, clinical grade preparations of rsTreg cells carries the risk of containing significant numbers of highly pathogenic recipient-specific effector T cells. We hypothesized that an alternative approach using Treg cells specific for an exogenous (i.e. nondonor, nonrecipient) Ag (exoTreg cells) can overcome this risk by taking advantage of the bystander suppressive effect of Treg cells. For this, we used a murine model for aggressive GVH disease. We expanded ex vivo exoTreg cells that are primed against the HY Ag, which is only expressed in males. ExoTreg cells supressed GVH disease as efficiently as rsTreg cells in recipient male mice. We also applied this strategy in female mice that do not express this Ag. While exoTreg cells were not effective in female recipients when applied alone, providing the cognate HY Ag in vivo along side effectively activated exoTreg cells and completely abrogated GVH disease, establishing a targeted on/off system to provide a suppressive effect on alloreactive effector T cells.
authors.affiliation: UPMC Univ Paris 06, CNRS UMR7211, INSERM U959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.
authors.forename: Gaëlle H
authors.initials: GH
authors.lastname: Martin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grégoire
authors.forename: Dan A
authors.initials: DA
authors.lastname: Landau
authors.forename: Caroline
authors.initials: C
authors.lastname: Pilon
authors.forename: Yenkel
authors.initials: Y
authors.lastname: Grinberg-Bleyer
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mège
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
authors.forename: Benoît L
authors.initials: BL
authors.lastname: Salomon
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
mesh_terms: D000818:Animals; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D006182:H-Y Antigen
keywords: GVH disease; Immune regulation; Inducible activation of regulatory T (Treg) cells; Tolerance; Transplantation