PMID- 20696947
OWN - NLM
STAT- MEDLINE
DCOM- 20101215
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 116
IP  - 18
DP  - 2010 Nov 4
TI  - When Toll-like receptor and T-cell receptor signals collide: a mechanism for 
      enhanced CD8 T-cell effector function.
PG  - 3494-504
LID - 10.1182/blood-2010-02-268169 [doi]
AB  - Emerging reports reveal that activating Toll-like receptor-2 (TLR2)-MyD88 signals 
      in CD8 T lymphocytes enhances cytokine production and cytotoxicity; however, the 
      signaling pathway remains undefined. In the present study, we examined the 
      physiologic significance and molecular mechanisms involved in this process. We 
      found that TLR2 engagement on T-cell receptor transgenic CD8 OT-1 T cells 
      increased T-bet transcription factor levels consequently, augmenting effector 
      transcript and protein levels both in vivo and in vitro. In contrast, TLR2 
      agonist did not costimulate TLR2(-/-)OT-1 or MyD88(-/-)OT-1 T cells. Elevated 
      T-bet levels in TLR2-MyD88-activated T cells was a consequence of increased 
      biosynthesis resulting from the enhanced activation of the mammalian target of 
      the rapamycin (mTOR) pathway. Inhibiting mTOR, Akt, or protein kinase C in T 
      cells abolished the costimulatory effects of the TLR2 agonist. In vivo, 
      activating TLR2-MyD88 signals in T cells increased effector-molecule levels and 
      enhanced the clearance of Listeria monocytogenes-Ova. These results help define a 
      signaling pathway linking the TLR-MyD88 and mTOR pathway in an Akt- and protein 
      kinase C-dependent manner. These results highlight a critical role for MyD88 
      signaling in T-cell activation and cytotoxicity. Furthermore, these findings 
      offer the opportunity for improving the efficacy of vaccines and T cell-based 
      immunotherapies by targeting TLR-MyD88 signaling within T cells.
FAU - Geng, Degui
AU  - Geng D
AD  - University of Maryland Greenebaum Cancer Center, 655 W. Baltimore Street, 
      Baltimore, MD 21201, USA.
FAU - Zheng, Liqin
AU  - Zheng L
FAU - Srivastava, Ratika
AU  - Srivastava R
FAU - Asprodites, Nicole
AU  - Asprodites N
FAU - Velasco-Gonzalez, Cruz
AU  - Velasco-Gonzalez C
FAU - Davila, Eduardo
AU  - Davila E
LA  - eng
GR  - P30 CA134274/CA/NCI NIH HHS/United States
GR  - R01 CA140917/CA/NCI NIH HHS/United States
GR  - P20 RR021970-027657/RR/NCRR NIH HHS/United States
GR  - 1P20RR021970/RR/NCRR NIH HHS/United States
GR  - P20 RR021970/RR/NCRR NIH HHS/United States
GR  - R01 CA140917-01/CA/NCI NIH HHS/United States
GR  - 1R01CA140917/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100809
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptors)
RN  - 126465-35-8 (Perforin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology/microbiology
MH  - Gene Expression Regulation
MH  - Granzymes/immunology
MH  - Interferon-gamma/genetics/immunology
MH  - Mice
MH  - Myeloid Differentiation Factor 88/immunology
MH  - Perforin/genetics/immunology
MH  - Phosphatidylinositol 3-Kinases/immunology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase C/antagonists & inhibitors/immunology
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - T-Box Domain Proteins/genetics/immunology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/immunology
MH  - Toll-Like Receptor 2/immunology
MH  - Toll-Like Receptors/*immunology
PMC - PMC2981476
EDAT- 2010/08/11 06:00
MHDA- 2010/12/16 06:00
PMCR- 2011/11/04
CRDT- 2010/08/11 06:00
PHST- 2010/08/11 06:00 [entrez]
PHST- 2010/08/11 06:00 [pubmed]
PHST- 2010/12/16 06:00 [medline]
PHST- 2011/11/04 00:00 [pmc-release]
AID - S0006-4971(20)31146-0 [pii]
AID - 2010/268169 [pii]
AID - 10.1182/blood-2010-02-268169 [doi]
PST - ppublish
SO  - Blood. 2010 Nov 4;116(18):3494-504. doi: 10.1182/blood-2010-02-268169. Epub 2010 
      Aug 9.