CD95 co-stimulation blocks activation of naive T cells by inhibiting T cell receptor signaling

CD95 is a multifunctional receptor that induces cell death or proliferation depending on the signal, cell type, and cellular context. Here, we describe a thus far unknown function of CD95 as a silencer of T cell activati
CD95 is a multifunctional receptor that induces cell death or proliferation depending on the signal, cell type, and cellular context. Here, we describe a thus far unknown function of CD95 as a silencer of T cell activation. Naive human T cells triggered by antigen-presenting cells expressing a membrane-bound form of CD95 ligand (CD95L) or stimulated by anti-CD3 and -CD28 antibodies in the presence of recombinant CD95L had reduced activation and proliferation, whereas preactivated, CD95-sensitive T cells underwent apoptosis. Triggering of CD95 during T cell priming interfered with proximal T cell receptor signaling by inhibiting the recruitment of ζ-chain–associated protein of 70 kD, phospholipase-γ, and protein kinase C-θ into lipid rafts, thereby preventing their mutual tyrosine protein phosphorylation. Subsequently, Ca2+ mobilization and nuclear translocation of transcription factors NFAT, AP1, and NF-κB were strongly reduced, leading to impaired cytokine secretion. CD95-mediated inhibition of proliferation in naive T cells could not be reverted by the addition of exogenous interleukin-2 and T cells primed by CD95 co-stimulation remained partially unresponsive upon secondary T cell stimulation. HIV infection induced CD95L expression in primary human antigeen-presenting cells, and thereby suppressed T cell activation, suggesting that CD95/CD95L-mediated silencing of T cell activation represents a novel mechanism of immune evasion.
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Metadaten
Author:Gudrun Strauss, Jonathan A. Lindquist, Nathalie Arhel, Edward Felder, Sabine Karl, Tobias L. Haas, Simone Fulda, Henning Walczak, Frank Kirchhoff, Klaus-Michael Debatin
URN:urn:nbn:de:hebis:30:3-243671
DOI:http://dx.doi.org/10.1084/jem.20082363
ISSN:1540-9538
ISSN:0022-1007
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=19487421
Parent Title (English):Journal of experimental medicine
Publisher:Rockefeller Univ. Press
Place of publication:New York, NY
Document Type:Article
Language:English
Date of Publication (online):2012/05/24
Date of first Publication:2009/06/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/05/24
Volume:206
Issue:6
Pagenumber:15
First Page:1379
Last Page:1393
HeBIS PPN:304051233
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen

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