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1 From the Department of Ophthalmology and Visual Science, Department of Pathology, and 2 The Committee on Immunology, University of Chicago, Illinois.
PURPOSE. To investigate the mechanism of action of the soluble immune suppressive product secreted by human fetal retinal pigment epithelial (HFRPE) cells in a model system using the human T-cell line Jurkat (Jkt).
METHODS. Pure HFRPE cells were isolated and cultured. The supernatants of both
nonactivated and IFN-
–activated HFRPE cells were isolated. Cells
from the human T-cell line Jkt were incubated either in standard
culture medium or in the supernatant isolated from HFRPE cells. In the
first assay Jkt cell proliferation was measured by
[3H]thymidine incorporation. In the second assay Jkt cell
apoptosis was examined for annexin V staining by flow cytometry. In the
third assay Jkt cell division was evaluated with carboxyfluorescein
succinimidyl ester (CFSE) fluorescent dye. In the last assay the
mitochondrial transmembrane potential of Jkt cells was measured with
the cationic lipophilic fluorochrome 3,3'-dihexyloxacarbocyanine iodide
[DiOC(6)]. In all the assays the effect of supernatants
isolated from both nonactivated and IFN-–activated HFRPE cells were
compared with standard culture medium. The involvement of antiapoptotic
human gene bcl-xLwas determined
by using a Jkt cell line that was stably transfected with
bcl-xL.
RESULTS. The supernatant isolated from HFRPE cells significantly suppressed the
cell division in Jkt cells and induced apoptosis. These effects were
stronger when the supernatant was isolated from IFN-–activated
HFRPE cells. The apoptosis pathway induced by the secreted product of
HFRPE cells involved the early disruption of mitochondrial
transmembrane potential. Although the overexpression of
bcl-xL gene rescued the Jkt cells
from supernatant-induced apoptosis, it could not restore the
proliferation of Jkt cells.
CONCLUSIONS. These data suggest that HFRPE cells secrete a product that initiates an early cell cycle arrest in the human T-cell line Jkt, which is followed by the activation of an apoptotic pathway that involves the loss of mitochondrial membrane potential. The latter could be prevented by bcl-xL overexpression. Also these data suggest that the HFRPE-induced T-cell apoptosis may play a significant role in maintaining the immune privilege in the subretinal space.
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