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Newly discovered role for Fas ligand in the cell-cycle arrest of CD4+ T cells

Nature Medicine volume 4, pages 1377–1382 (1998)Cite this article

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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Figure 1: FasL signaling inhibits CD4+ T-cell proliferation and blastogenesis.
Figure 2: FasL engagement results in early cell-cycle arrest followed by apoptosis.
Figure 3: FasL engagement inhibits the upregulation of activation molecules and cell-cycle regulatory proteins.
Figure 4: FasL engagement inhibits CD4+ T-cell proliferation by inhibiting IL-2 production.
Figure 5: FasL engagement inhibits the proliferation of wild-type, lpr and lprcg, but not gld, CD4+ T cells.
Figure 6: Soluble FasFc blocks endogenous FasL-mediated inhibition of proliferation in lprcg, but not lpr and gld, cells.
Figure 7: FasL engagement prevents CD4+ T cell expansion in response to superantigens in vivo.

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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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Authors and Affiliations

  1. Division of Immunobiology, Department of Medicine University of Vermont College of Medicine, Burlington, 05405, Vermont, USA

    Julie Desbarats & M. Karen Newell

  2. Departments of Medicine and Immunology, Shreve Laboratory for Tumor Immunology, University of Colorado Cancer Center, Denverm, 80262, Colorado, USA

    Richard C. Duke

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  1. Julie Desbarats
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Correspondence to M. Karen Newell.

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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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