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. 2015 Jan;293(1):30-3.
doi: 10.1016/j.cellimm.2014.11.007. Epub 2014 Dec 6.

Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection

Robert J Plenter  1 , Todd J Grazia  2 , David P Nelson  3 , Martin R Zamora  4 , Ronald G Gill  5 , Biagio A Pietra  6
Affiliations

Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection

Robert J Plenter et al. Cell Immunol. 2015 Jan.

Abstract

Fas Ligand limits inflammatory injury and permits allograft survival by inducing apoptosis of Fas-bearing lymphocytes. Previous studies have shown that the CD4(+) T-cell is both sufficient and required for murine cardiac allograft rejection. Here, utilizing a transgenic mouse that over-expresses Fas Ligand specifically on cardiomyocytes as heart donors, we sought to determine if Fas Ligand on graft parenchymal cells could resist CD4(+) T-cell mediated rejection. When transplanted into fully immunocompetent BALB/c recipients Fas Ligand transgenic hearts were acutely rejected. However, when transplanted into CD4(+) T-cell reconstituted BALB/c-rag(-/-) recipients, Fas Ligand hearts demonstrated long-term survival. These results indicate that Fas Ligand over-expression on cardiomyocytes can indeed resist CD4(+) T-cell mediated cardiac rejection and suggests contact dependence between Fas Ligand expressing graft parenchymal cells and the effector CD4(+) T-cells.

Keywords: Fas Ligand; Rejection; Transplantation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1. FVB control cardiac allografts and FasL cardiac allografts are acutely rejected
FVB (●) and FasL (■) cardiac allografts are rejected in very similar tempo when transplanted into BALB/c (H-2d) wild type recipients.
Fig. 2
Fig. 2. FasL over-expressing cardiac allografts survive indefinitely in BALB/c-rag-/-recipients reconstituted with BALB/c CD4+ T-cells
Donor hearts from FasL mice survived indefinitely in BALB/c-rag-/- mice that had been reconstituted with purified CD4+ T-cells (▲) while FVB hearts were rejected in CD4+ T-cell reconstituted C.B-17 scid (H-2d) recipients (◆).
Fig. 3
Fig. 3. a and b FasL over-expressing cardiac allografts do not contain graft destructive cells
a. Histology of a graft that has been acutely rejected displays extensive mononuclear cell infiltration and evidence of necrosis and hemorrhage. b. A long-term surviving FasL heart in a CD4+ T-cell reconstituted BALB/c-rag-/- recipient demonstrating graft infiltrating mononuclear cells in the ventricular endocardium, but a paucity of infiltrating cells in the myocardium.
See this image and copyright information in PMC

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