title: Fibrinogen-like protein 2/fibroleukin induces long-term allograft survival in a rat model through regulatory B cells.
abstract: We previously described that in a rat model of heart transplantation tolerance was dependent on CD8+CD45RClow Tregs that over-expressed fibrinogen-like protein 2 (FGL2)/fibroleukin. Little is known on the immunoregulatory properties of FGL2. Here we analyzed the transplantation tolerance mechanisms that are present in Lewis 1A rats treated with FGL2. Over-expression of FGL2 in vivo through adenovirus associated virus -mediated gene transfer without any further treatment resulted in inhibition of cardiac allograft rejection. Adoptive cell transfer of splenocytes from FGL2-treated rats with long-term graft survival (> 80 days) in animals that were transplanted with cardiac allografts inhibited acute and chronic organ rejection in a donor-specific and transferable tolerance manner, since iterative adoptive transfer up to a sixth consecutive recipient resulted in transplantation tolerance. Adoptive cell transfer also efficiently inhibited anti-donor antibody production. Analysis of all possible cell populations among splenocytes revealed that B lymphocytes were sufficient for this adoptive cell tolerance. These B cells were also capable of inhibiting the proliferation of CD4+ T cells in response to allogeneic stimuli. Moreover, gene transfer of FGL2 in B cell deficient rats did not prolong graft survival. Thus, this is the first description of FGL2 resulting in long-term allograft survival. Furthermore, allograft tolerance was transferable and B cells were the main cells responsible for this effect.
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Bézie
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Picarda
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tesson
authors.affiliation: Centre Hospitalier Universitaire de Nantes, Faculté de Médecine. Nantes, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Renaudin
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Durand
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Ménoret
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mérieau
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Chiffoleau
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Guillonneau
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Caron
authors.affiliation: INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
mesh_terms: D064591:Allografts / Q000637:transplantation*; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism*; D005340:Fibrinogen / Q000008:administration & dosage* / Q000235:genetics; D018014:Gene Transfer Techniques; D006084:Graft Rejection / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000628:therapy*; D006085:Graft Survival; D008297:Male; D051381:Rats
chemical_list: C585327:fibrinogen-like protein 2, rat; D005340:Fibrinogen