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PLoS One. 2015 Mar 12;10(3):e0119686. doi: 10.1371/journal.pone.0119686. eCollection 2015.

Fibrinogen-like protein 2/fibroleukin induces long-term allograft survival in a rat model through regulatory B cells.

Author information

1
INSERM UMR 1064-ITUN, Centre Hospitalier Universitaire de Nantes, Faculté de Médecine, Nantes, France.
2
Centre Hospitalier Universitaire de Nantes, Faculté de Médecine. Nantes, France.

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.

PMID:
25763980
PMCID:
PMC4357433
DOI:
10.1371/journal.pone.0119686
[Indexed for MEDLINE]
Free PMC Article

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