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

PloS One
Séverine BézieIgnacio Anegon

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, gen...Continue Reading

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Citations

Sep 22, 2015·The Journal of Clinical Investigation·Séverine BézieCarole Guillonneau
Jan 13, 2018·Frontiers in Cellular and Infection Microbiology·Ala E TaborNicholas N Jonsson
Apr 25, 2018·Transplantation·Séverine BézieCarole Guillonneau
Oct 9, 2019·Immunological Reviews·Léa FlippeCarole Guillonneau
Nov 11, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Séverine BézieCarole Guillonneau
Jan 1, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A BartczakG A Levy
Mar 16, 2021·Frontiers in Immunology·Leila AminiIgnacio Anegon
Sep 27, 2020·Cellular Immunology·Jason R Lees
Jan 9, 2021·Transplantation·Xinle WangCatia T Perciani

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Methods Mentioned

BETA
transfection
PCR
electrophoresis
FACS
flow cytometry

Software Mentioned

FACS Aria
GraphPad Prism
FLOWJO

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