PMID- 15944259
OWN - NLM
STAT- MEDLINE
DCOM- 20050831
LR  - 20220409
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 174
IP  - 12
DP  - 2005 Jun 15
TI  - TCR engagement increases hypoxia-inducible factor-1 alpha protein synthesis via 
      rapamycin-sensitive pathway under hypoxic conditions in human peripheral T cells.
PG  - 7592-9
AB  - Peripheral T cells encounter rapid decrease in oxygen tension because they are 
      activated by Ag recognition and migrate into inflammatory sites or tumors. 
      Activated T cells, therefore, are thought to have such machineries that enable 
      them to adapt to hypoxic conditions and execute immune regulation in situ. We 
      have recently shown that survival of CD3-engaged human peripheral blood T cells 
      is prolonged under hypoxic conditions and hypoxia-inducible factor-1 (HIF-1) and 
      its target gene product adrenomedullin play a critical role for the process. It 
      is also shown that hypoxia alone is not sufficient, but TCR-mediated signal is 
      required for accumulation of HIF-1alpha in human peripheral T cells. In the 
      present study, we showed that TCR engagement does not influence hypoxia-dependent 
      stabilization but stimulates protein synthesis of HIF-1alpha, most possibly via 
      PI3K/mammalian target of rapamycin system, and that expression of HIF-1alpha and 
      its target genes is blocked by treatment with rapamycin. Since some of those gene 
      products, e.g., glucose transporters and phosphoglycerokinase, are considered to 
      be essential for glycolysis and energy production under hypoxic conditions and 
      adequate immune reaction in T cells, this TCR-mediated synthesis of HIF-1alpha 
      may play a pivotal role in peripheral immune response. Taken together, our 
      results may highlight a novel aspect of downstream signal from Ag recognition by 
      TCR and a unique pharmacological role of rapamycin as well.
FAU - Nakamura, Hiroshi
AU  - Nakamura H
AD  - Division of Clinical Immunology, Advanced Clinical Research Center, Institute of 
      Medical Science, University of Tokyo, Tokyo, Japan.
FAU - Makino, Yuichi
AU  - Makino Y
FAU - Okamoto, Kensaku
AU  - Okamoto K
FAU - Poellinger, Lorenz
AU  - Poellinger L
FAU - Ohnuma, Kei
AU  - Ohnuma K
FAU - Morimoto, Chikao
AU  - Morimoto C
FAU - Tanaka, Hirotoshi
AU  - Tanaka H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD3 Complex)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - CD3 Complex/metabolism
MH  - Cell Hypoxia/drug effects/genetics/immunology
MH  - Cells, Cultured
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Jurkat Cells
MH  - Phosphatidylinositol 3-Kinases/blood/physiology
MH  - Protein Kinases/blood/physiology
MH  - Receptors, Antigen, T-Cell/blood/metabolism/*physiology
MH  - Signal Transduction/genetics/*immunology
MH  - Sirolimus/*pharmacology
MH  - T-Lymphocyte Subsets/drug effects/*immunology/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/antagonists & inhibitors/*biosynthesis/blood/genetics
MH  - Transfection
EDAT- 2005/06/10 09:00
MHDA- 2005/09/01 09:00
CRDT- 2005/06/10 09:00
PHST- 2005/06/10 09:00 [pubmed]
PHST- 2005/09/01 09:00 [medline]
PHST- 2005/06/10 09:00 [entrez]
AID - 174/12/7592 [pii]
AID - 10.4049/jimmunol.174.12.7592 [doi]
PST - ppublish
SO  - J Immunol. 2005 Jun 15;174(12):7592-9. doi: 10.4049/jimmunol.174.12.7592.