Abstract
Fas Ligand (FasL) can induce apoptosis of Fas-bearing cells. It is expressed on the cell surface of many tumor cells, immune-privileged tissues and activated lymphocytes. We report here that FasL can itself transduce signals, leading to cell-cycle arrest and cell death in CD4+ T cells. In vitro, FasL engagement inhibited CD4+ T-cell proliferation, cell-cycle progression, and IL-2 secretion. In vivo, FasL engagement prevented superantigen-mediated CD4+, but not CD8+, T-cell expansion. These findings demonstrate that FasL engagement regulates cell-cycle progression, and show that FasL engagement in vivo has a potent anti-inflammatory effect specific for CD4+ T cells.
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Acknowledgements
We thank R. Budd and M. Coggeshall for their reviews of the manuscript,, J.E. Stone for technical assistance, C. Charland for flow cytometry, and R. Christie for secretarial assistance. Funding for these studies was provided by NIH ROI AI33470 (M.K.N), and USPHS-NIH AI40394 and AI40607 (R.C.D.). J.D. is supported by a Medical Research Council of Canada fellowship.
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Desbarats, J., Duke, R. & Newell, M. Newly discovered role for Fas ligand in the cell-cycle arrest of CD4+ T cells. Nat Med 4, 1377–1382 (1998). https://doi.org/10.1038/3965
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DOI: https://doi.org/10.1038/3965
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