Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Maximal Proliferation of Cytotoxic T Lymphocytes Requires Reverse Signaling through Fas Ligand

Maximal Proliferation of Cytotoxic T Lymphocytes Requires Reverse Signaling through Fas Ligand Fas ligand (FasL/CD95L) is best known for its role in delivering apoptotic signals through its receptor, Fas (APO-1/CD95). In this study, we present evidence that FasL has a second role as a signaling receptor. Alloantigen-specific proliferation by multiple FasL − murine CTL lines is depressed compared to that of FasL + CTL lines. FasL − CTLs kill efficiently on a per recovered cell basis and can achieve wild-type levels of proliferation upon stimulation by optimal doses of anti-CD3, suggesting the lack of a costimulatory signal during antigen stimulation. To test this hypothesis directly, soluble FasIgG, a fusion protein of murine Fas and human IgG 1 , was added to FasL + CTLs to demonstrate that blocking cell surface Fas–FasL interactions mimics the depression observed for FasL − CTLs. In addition, plate-bound FasIgG in conjunction with suboptimal anti-CD3 stimulation augments proliferative signals in FasL + but not FasL − CTLs. In contrast to these results with CD8 + T cells, alloantigen-stimulated FasL − CD4 + T cells proliferate vigorously compared to FasL + cells. These data demonstrate that reverse signaling through FasL is required for CTLs to achieve maximal proliferation and may provide clues to differences in the homeostatic regulation of activated CD4 + and CD8 + T cells during an immune response. Footnotes Submitted: 4 August 1997 Revision received 29 October 1997 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

Maximal Proliferation of Cytotoxic T Lymphocytes Requires Reverse Signaling through Fas Ligand

Suzuki, Ivy; Fink, Pamela J.
The Journal of Experimental Medicine , Volume 187 (1): 123 – Jan 5, 1998
Download PDF
6 pages

Loading next page...
 
/lp/rockefeller-university-press/maximal-proliferation-of-cytotoxic-t-lymphocytes-requires-reverse-OuZy0Enj5C

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
Rockefeller University Press
Copyright
© 1998 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.187.1.123
Publisher site
See Article on Publisher Site

Abstract

Fas ligand (FasL/CD95L) is best known for its role in delivering apoptotic signals through its receptor, Fas (APO-1/CD95). In this study, we present evidence that FasL has a second role as a signaling receptor. Alloantigen-specific proliferation by multiple FasL − murine CTL lines is depressed compared to that of FasL + CTL lines. FasL − CTLs kill efficiently on a per recovered cell basis and can achieve wild-type levels of proliferation upon stimulation by optimal doses of anti-CD3, suggesting the lack of a costimulatory signal during antigen stimulation. To test this hypothesis directly, soluble FasIgG, a fusion protein of murine Fas and human IgG 1 , was added to FasL + CTLs to demonstrate that blocking cell surface Fas–FasL interactions mimics the depression observed for FasL − CTLs. In addition, plate-bound FasIgG in conjunction with suboptimal anti-CD3 stimulation augments proliferative signals in FasL + but not FasL − CTLs. In contrast to these results with CD8 + T cells, alloantigen-stimulated FasL − CD4 + T cells proliferate vigorously compared to FasL + cells. These data demonstrate that reverse signaling through FasL is required for CTLs to achieve maximal proliferation and may provide clues to differences in the homeostatic regulation of activated CD4 + and CD8 + T cells during an immune response. Footnotes Submitted: 4 August 1997 Revision received 29 October 1997

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: Jan 5, 1998

References

  • The fas death factor
    Nagata
  • Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas
    Gruss
  • The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death
    Smith
  • Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells
    Stuber
  • Reverse signaling viaCD30 ligand
    Wiley
  • Fas involvement in Ca2+-independent T cell–mediated cytotoxicity
    Rouvier
  • Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells
    Ceredig
  • IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt-2 antigen block T cell-mediated cytolysis in the absence of complement
    Sarmiento
  • Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens
    Ozato
  • Fas(CD95)/FasL interactions required for programmed cell death after T cell activation
    Ju
  • Cell-autonomous Fas(CD95)/ Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas
    Brunner
  • Autocrine T-cell suicide mediated by APO-1/ (Fas/CD95)
    Dhein
  • The mouse Fas-ligand gene is mutated in gldmice and is part of a TNF family gene cluster
    Lynch
  • Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand
    Takahashi
  • Identification of a ten–amino acid proline-rich SH3 binding site
    Ren
  • Induction of apoptosis in mature T cells by tumour necrosis factor
    Zheng
  • Different susceptibility of cytotoxic T cells to CD95 (Fas/Apo-1) ligand–mediated cell death after activation in vitro versus in vivo.
    Ehl
  • The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice
    Sytwu
  • Fas ligand–mediated cytotoxicity is directly responsible for apoptosis of normal CD4+T cells responding to a bacterial superantigen
    Ettinger
  • Autoimmune gldmutation uncouples suicide and cytokine/proliferation pathways in activated, mature T cells
    Russell
  • Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor
    Rathmell
  • Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells
    Rothstein
  • Generation of memory B cells and plasma cells in vitro.
    Arpin
  • T cell receptor antagonist peptides induce positive selection
    Hogquist
  • Fas transduces activation signals in normal human T lymphocytes
    Alderson
  • APO-1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl-2 oncogene expression
    Mapara
  • Recent advances in tumor necrosis factor and CD40 signaling
    Tewari
  • Two TNF receptors
    Tartaglia
  • Induction of nuclear factor κB by the CD30 receptor is mediated by TRAF1 and TRAF2
    Duckett
  • CTLA-4 can function as a negative regulator of T cell activation
    Walunas