Reverse signaling by FasL inhibits primary human T cell activation
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BioMed Central
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Meeting abstract
Reverse signaling by FasL inhibits primary human T cell activation M Paulsen*, S Valentin and O Janssen Address: UK-SH Campus Kiel, Institute of Immunology, Molecular Immunology, Kiel, Germany * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A23
doi:10.1186/1478-811X-7-S1-A23
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.This abstract is available from: http://www.biosignaling.com/content/7/S1/A23 © 2009 Paulsen et al; licensee BioMed Central Ltd.
The death-factor Fas Ligand (FasL) is best known for its capacity to induce cell death in Fas-expressing cells. Besides its death-promoting activity, FasL has been implicated in reverse signaling and might thus also play a role in T cell development and selection and the modulation of T cell activation by acting as a costimulatory receptor. Here we have analyzed the influence of FasL-costimulation on TCR/CD3/CD28-triggered activation of peripheral human T-lymphocytes. Interestingly, FasL engagement inhibited the proliferation of PBMC, CD8+ as well as CD4+ T cells. Plate-bound but not soluble FasFc fusion protein or anti-FasL pAb blocked CD3/CD28induced proliferation almost completely. We observed not only less proliferation, but also decreased IL-2 production and reduced expression of the activation markers CD69 and CD25. Importantly, FasFc costimulation also resulted in a dramatic inhibition of TCR internalization, thereby preventing TCR translocation and the formation of signaling platforms essential for optimal T cell activation. Consistent with these findings, various crucial signaling components of the T cell receptor activation pathway were inhibited by FasL triggering and reverse signalling. In this context, the phosphorylation of ERK1/2, p38 MAPK as well as further upstream acting signaling proteins such as PLCγ was markedly reduced. Notably, the inhibition was also observed in the presence of exogenous rIL-2, indicating that a lack of IL-2 is not the cause of the proliferation block. Taken together, our data argue for a negative reverse signaling capacity of FasL on freshly isolated, TCR-triggered human T cells.
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