PMID- 21268004
OWN - NLM
STAT- MEDLINE
DCOM- 20110405
LR  - 20171116
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 41
IP  - 2
DP  - 2011 Feb
TI  - TNFR1 delivers pro-survival signals that are required for limiting 
      TNFR2-dependent activation-induced cell death (AICD) in CD8+ T cells.
PG  - 335-44
LID - 10.1002/eji.201040639 [doi]
AB  - Members of the TNF and TNF receptor (TNFR) superfamily play important roles in 
      the maintenance of homeostasis of the immune system. Furthermore, several members 
      of the TNFR family participate in T-cell activation and sustaining T-cell 
      responses. We have shown that TNFR2 regulates T-cell activation by lowering the 
      activation threshold and providing costimulatory signaling. Furthermore, 
      activated TNFR2(-/-) CD8(+) T cells are highly resistant to activation-induced 
      cell death (AICD). Here, we showed that using anti-TNFR2 antibodies to block 
      TNFR2 on activated WT CD8(+) T cells rendered them resistant to AICD. This 
      resistance of activated TNFR2(-/-) CD8(+) T cells to AICD correlated with the 
      accumulation of TNF receptor-associated factor 2 (TRAF2). Overexpression of TRAF2 
      by retroviral transfection and knockdown of TRAF2 by small interfering RNA also 
      support this conclusion. Furthermore, neutralizing TNF-alpha reduced TRAF2 
      accumulation in activated TNFR2(-/-) CD8(+) T cells and increased their 
      susceptibility to AICD. AICD-resistant TNFR2(-/-) CD8(+) T cells expressed 
      elevated levels of phosphorylated IkappaBalpha and higher DNA-binding activity of the p65 
      NK-kappaB subunit and neutralization of TNF-alpha blocked this increase. Therefore, in 
      activated TNFR2(-/-) CD8(+) T cells, TNFR1 functions as a survival receptor by 
      utilizing high intracellular levels of TRAF2 to promote IkappaBalpha phosphorylation and 
      NF-kappaB activation.
CI  - Copyright (c) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Twu, Yuh-Ching
AU  - Twu YC
AD  - Department of Microbiology and Immunology, University of British Columbia, 
      Vancouver, BC, Canada.
FAU - Gold, Michael R
AU  - Gold MR
FAU - Teh, Hung-Sia
AU  - Teh HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101229
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Antibodies)
RN  - 0 (CD3 Complex)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-2)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Rela protein, mouse)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
SB  - IM
MH  - Animals
MH  - Antibodies/immunology/pharmacology
MH  - Apoptosis/drug effects/genetics/*immunology
MH  - CD3 Complex/immunology
MH  - CD8-Positive T-Lymphocytes/*cytology/drug effects/*metabolism
MH  - Cell Death/drug effects/genetics/immunology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects/genetics/immunology
MH  - Gene Expression/genetics
MH  - I-kappa B Proteins/metabolism
MH  - Interleukin-2/pharmacology
MH  - Lymphocyte Activation/drug effects/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Phosphorylation/drug effects
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Tumor Necrosis Factor, Type I/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/genetics/immunology/*metabolism
MH  - Signal Transduction/drug effects/genetics/*immunology
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Transduction, Genetic
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism/pharmacology
EDAT- 2011/01/27 06:00
MHDA- 2011/04/06 06:00
CRDT- 2011/01/27 06:00
PHST- 2010/05/04 00:00 [received]
PHST- 2010/10/05 00:00 [revised]
PHST- 2010/11/04 00:00 [accepted]
PHST- 2011/01/27 06:00 [entrez]
PHST- 2011/01/27 06:00 [pubmed]
PHST- 2011/04/06 06:00 [medline]
AID - 10.1002/eji.201040639 [doi]
PST - ppublish
SO  - Eur J Immunol. 2011 Feb;41(2):335-44. doi: 10.1002/eji.201040639. Epub 2010 Dec 
      29.