PMID- 23380742
OWN - NLM
STAT- MEDLINE
DCOM- 20130528
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 121
IP  - 14
DP  - 2013 Apr 4
TI  - Notch controls generation and function of human effector CD8+ T cells.
PG  - 2638-46
LID - 10.1182/blood-2012-07-442962 [doi]
AB  - The generation of effector CD8(+) T cells with lytic capacity is crucial for 
      tumor control. Dendritic cells (DCs) provide important signals to promote naive 
      CD8(+) T cell priming and activation of effector T cells. Here, we report that 
      the Notch pathway has an important role in both these processes in human CD8(+) T 
      cells. Activated monocyte-derived DCs express Notch ligands Jagged1 and 
      Delta-like4, whereas naive CD8(+) T cells express Notch2. The role for Notch 
      signaling in CD8(+) T cell priming was determined using an ex-vivo model system 
      in which tumor antigen-specific primary CD8(+) T cell responses were measured. 
      Inhibition of Notch using gamma-secretase inhibitors or soluble Delta-like4-Fc during 
      activation reduced expansion of antigen-specific CD8(+) T cells, which was 
      mirrored by decreased frequencies of interferon (IFN)gamma-, tumor necrosis 
      factor-alpha-, and granzymeB-producing CD8(+) T cells. Moreover, T cells primed when 
      Notch signaling was prevented are functionally low-avidity T cells. In addition, 
      Notch partially regulates established effector T cell function. 
      Activation-induced Notch signaling is needed for IFNgamma release but not for 
      cytolytic activity. These data indicate that Notch signaling controls human 
      CD8(+) T cell priming and also influences effector T cell functions. This may 
      provide important information for designing new immunotherapies for treatment of 
      cancer.
FAU - Kuijk, Loes M
AU  - Kuijk LM
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical Center 
      Amsterdam, Amsterdam, The Netherlands.
FAU - Verstege, Marleen I
AU  - Verstege MI
FAU - Rekers, Niels V
AU  - Rekers NV
FAU - Bruijns, Sven C
AU  - Bruijns SC
FAU - Hooijberg, Erik
AU  - Hooijberg E
FAU - Roep, Bart O
AU  - Roep BO
FAU - de Gruijl, Tanja D
AU  - de Gruijl TD
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
FAU - Unger, Wendy W J
AU  - Unger WW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130204
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (MART-1 Antigen)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (NOTCH2 protein, human)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Receptor, Notch2)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigen Presentation/immunology
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism
MH  - Cell Communication/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/immunology/metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Lymphocyte Activation/*immunology
MH  - MART-1 Antigen/immunology/metabolism
MH  - Monocytes/cytology/immunology/metabolism
MH  - Neoplasms/immunology/prevention & control
MH  - Receptor, Notch1/*immunology/metabolism
MH  - Receptor, Notch2/*immunology/metabolism
MH  - Signal Transduction/*immunology
EDAT- 2013/02/06 06:00
MHDA- 2013/05/29 06:00
CRDT- 2013/02/06 06:00
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/05/29 06:00 [medline]
AID - S0006-4971(20)47361-6 [pii]
AID - 10.1182/blood-2012-07-442962 [doi]
PST - ppublish
SO  - Blood. 2013 Apr 4;121(14):2638-46. doi: 10.1182/blood-2012-07-442962. Epub 2013 
      Feb 4.