June 1999
Volume 40, Issue 7
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Articles  |   June 1999
Human fetal retinal pigment epithelial cells induce apoptosis in the T-cell line Jurkat.
Author Affiliations
  • L Farrokh-Siar
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • K A Rezai
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • R T Semnani
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • S C Patel
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • J T Ernest
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • E J Peterson
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • G A Koretzky
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
  • G A van Seventer
    Department of Ophthalmology and Visual Science, University of Chicago, Illinois 60637, USA.
Investigative Ophthalmology & Visual Science June 1999, Vol.40, 1503-1511. doi:
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    • Get Citation

      L Farrokh-Siar, K A Rezai, R T Semnani, S C Patel, J T Ernest, E J Peterson, G A Koretzky, G A van Seventer; Human fetal retinal pigment epithelial cells induce apoptosis in the T-cell line Jurkat.. Invest. Ophthalmol. Vis. Sci. 1999;40(7):1503-1511.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

PURPOSE: To investigate the mechanism(s) involved in human fetal retinal pigment epithelium (HFRPE)-mediated T-cell death. METHODS: Pure HFRPE cells were isolated and cultured. Normal and interferon (IFN)-gamma-activated HFRPE from early and late in vitro passages were incubated with cells from the human T-cell leukemia line Jurkat (Jkt). Cultures were pulsed with [3H]-thymidine to measure Jkt cell proliferation. Jkt cells were evaluated for apoptosis either by staining with an ethidium bromide/acridine orange mixture (AO/EB) or with Annexin V-phycoerythrin. The role of Fas ligand (FasL) molecule in HFRPE-mediated apoptosis was assessed by using a mutant Jkt cell line (DD3), which is deficient in Fas-mediated signaling. The involvement of the antiapoptotic human gene bcl-xL was determined by using Jkt cells that were stably transfected with bcl-x(L). The role of cell- cell contact in the induction of apoptosis was evaluated in a transwell system in the presence or absence of neutralizing antibodies against IFN-gamma and tumor necrosis factor (TNF)-alpha. RESULTS: HFRPE cells inhibited the proliferation of Jkt cells by inducing apoptosis through a FasL-independent pathway. Passaging and IFN-gamma activation strengthened the inhibitory effect of HFRPE cells on the proliferation of Jkt cells. At lower HFRPE passages (P2), bcl-alphaL, overexpression rescued the HFRPE cell-mediated apoptosis. The separation of the cells by the transwell system did not affect the HFRPE cell-mediated suppression. This suppressive effect was not mediated by the secretion of IFN-gamma or TNF-alpha molecules. CONCLUSIONS: HFRPE cells suppressed the proliferation of Jkt cells by inducing apoptosis. HFRPE cells induced a stronger inhibitory effect on Jkt cells at higher in vitro passages. The HFRPE-induced apoptosis was not mediated through the FasL/Fas pathway or through the secretion of the apoptosis-inducing cytokines IFN-gamma and TNF-alpha. The bcl-xL gene may play a role in preventing HFRPE cell-induced apoptosis in Jkt cells. These combined results suggest that the HFRPE-mediated suppression of primary T cells may also be mediated by the induction of apoptosis. Therefore, the retinal pigment epithelium may play a role in the induction of immune privilege in the subretinal space.

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