International Immunology Advance Access originally published online on March 30, 2009
International Immunology 2009 21(5):587-598; doi:10.1093/intimm/dxp028
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FasL cross-linking inhibits activation of human peripheral T cells
Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Arnold-Heller-Strasse 3, Building 17, D-24105 Kiel, Germany
Correspondence to: O. Janssen; E-mail: ojanssen{at}email.uni-kiel.de
Activation of resting T cells in vitro is triggered by combined TCR and CD28 engagement and can be modulated by simultaneous ligation of various other surface receptors. Although the Fas ligand (FasL) is best known for its capacity to initiate cell death in Fas-bearing cells, it has recently been implicated in the regulation of T cell activation. Thus, a cross-talk between the TCR and FasL is likely, but far from being biochemically elucidated. We now report that FasL engagement by immobilized but not soluble FasFc fusion protein and anti-FasL polyclonal antibody blocks the activation of human peripheral T cells even in the presence of CD28 co-stimulation. The data presented here stress the importance of the Fas/FasL system for signal initiation via the TCR–CD3 complex and provide further arguments for a retrograde signaling capacity of FasL or a crucial role of Fas as a co-stimulatory molecule.
Keywords: cell activation, co-stimulation, CD95L, FasFc, signal transduction
* These authors contributed equally to this study. The work forms part of the PhD Thesis of M.P. and the MD Thesis of B.M.
Received 18 March 2008, accepted 23 February 2009.