NDLI: Fibrinogen-Like Protein 2/Fibroleukin Induces Long-Term Allograft Survival in a Rat Model through Regulatory B Cells

Content Provider	PubMed Central
Author	Bézie, Séverine Elodie, Picarda Tesson, Laurent Renaudin, Karine Durand, Justine Ménoret, Séverine Emmanuel, Mérieau Elise, Chiffoleau Carole, Guillonneau Caron, Lise Anegon, Ignacio
Editor	Lucienne, Chatenoud
Copyright Year	2015
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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0119686
Starting Page	119686
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	3
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-03-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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