PMID- 25476730
OWN - NLM
STAT- MEDLINE
DCOM- 20150508
LR  - 20211203
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 45
IP  - 3
DP  - 2015 Mar
TI  - mTOR signaling promotes a robust and continuous production of IFN-gamma by human 
      memory CD8+ T cells and their proliferation.
PG  - 893-902
LID - 10.1002/eji.201445086 [doi]
AB  - Human CD8(+) T cells are functionally heterogeneous and can be divided into 
      phenotypically and functionally distinct subsets according to CCR7 and CD45RA 
      expression levels. Among these, CCR7(low) CD45RA(low) effector memory CD8(+) T 
      cells (Tem) and CCR7(low) CD45RA(high) CD8(+) T cells, which are designated as 
      Temra and considered to be terminally differentiated cells, are Ag-experienced T 
      cells but show different functionalities. Here, we show that, while Tem 
      proliferate vigorously and produce IFN-gamma persistently and robustly, Temra 
      proliferate poorly and lose the ability to produce IFN-gamma over time after TCR 
      stimulation. Temra showed impaired cell growth upon TCR stimulation, which was 
      associated with defective activation of the mammalian target of rapamycin (mTOR) 
      signaling. Furthermore, rapamycin, an inhibitor of mTOR signaling, interfered 
      with the robust and continuous proliferation of and IFN-gamma production by Tem at 
      later time points after TCR stimulation. Thus, these data collectively indicate 
      that activation of mTOR signaling is required for the robust functions of Tem 
      cells in humans and suggest that defective mTOR signaling in Temra contributes to 
      their functional impairment.
CI  - (c) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Setoguchi, Ruka
AU  - Setoguchi R
AD  - Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate 
      School of Medicine, Kyoto University, Kyoto, Japan.
FAU - Matsui, Yui
AU  - Matsui Y
FAU - Mouri, Kousuke
AU  - Mouri K
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150102
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (CCR7 protein, human)
RN  - 0 (IFNG protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, CCR7)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - *Cell Proliferation
MH  - Female
MH  - Humans
MH  - *Immunologic Memory
MH  - Immunosuppressive Agents/pharmacology
MH  - Interferon-gamma/*immunology
MH  - Leukocyte Common Antigens/immunology
MH  - Male
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Receptors, CCR7/immunology
MH  - Signal Transduction/drug effects/*immunology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*immunology
OTO - NOTNLM
OT  - CCR7
OT  - CD45RA
OT  - CD8+ T cells
OT  - IFN-gamma
OT  - mTOR signaling
EDAT- 2014/12/06 06:00
MHDA- 2015/05/09 06:00
CRDT- 2014/12/06 06:00
PHST- 2014/07/31 00:00 [received]
PHST- 2014/10/29 00:00 [revised]
PHST- 2014/12/01 00:00 [accepted]
PHST- 2014/12/06 06:00 [entrez]
PHST- 2014/12/06 06:00 [pubmed]
PHST- 2015/05/09 06:00 [medline]
AID - 10.1002/eji.201445086 [doi]
PST - ppublish
SO  - Eur J Immunol. 2015 Mar;45(3):893-902. doi: 10.1002/eji.201445086. Epub 2015 Jan 
      2.