TY  - JOUR
A1  - Strauss, Gudrun
A1  - Lindquist, Jonathan A.
A1  - Arhel, Nathalie
A1  - Felder, Edward
A1  - Karl, Sabine
A1  - Haas, Tobias L.
A1  - Fulda, Simone
A1  - Walczak, Henning
A1  - Kirchhoff, Frank
A1  - Debatin, Klaus-Michael
T1  - CD95 co-stimulation blocks activation of naive T cells by inhibiting T cell receptor signaling
T2  - Journal of experimental medicine
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24367
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-243671
SN  - 1540-9538
SN  - 0022-1007
VL  - 206
IS  - 6
SP  - 1379
EP  - 1393
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -