PMID- 17055754
OWN - NLM
STAT- MEDLINE
DCOM- 20061222
LR  - 20220224
IS  - 1074-7613 (Print)
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Linking)
VI  - 25
IP  - 5
DP  - 2006 Nov
TI  - The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4+ T cells and 
      enables CpG oligodeoxynucleotide-mediated costimulation.
PG  - 783-93
AB  - While T cells respond directly to toll-like receptor (TLR) agonists, 
      TLR-signaling pathways in T cells are poorly characterized. Here we demonstrate 
      in CD4(+) T cells that CpG DNA directly enhances proliferation, prevents anergy, 
      and augments humoral responses to a T cell-dependent antigen by a Myeloid 
      differentiation primary-response protein 88 (MyD88) and Phosphatidylinositol 
      3-kinase (PI-3 kinase)-dependent pathway. PI-3 kinase activation required a 
      putative Src-homology domain (SH2) binding motif in the MyD88 Toll-Like or IL-1 
      Receptor (TIR) domain. Reconstitution of MyD88-deficient primary T cells with a 
      MyD88 transgene mutated in this motif abrogated association of PI-3 kinase with 
      MyD88, phosphorylation of protein kinase B (Akt) and Glycogen Synthetase Kinase-3 
      (GSK-3), and interleukin-2 (IL-2) production. The MyD88 death domain, on the 
      other hand, was required for NF-kB activation and survival. These studies 
      identify a MyD88-dependent PI-3 kinase-signaling pathway in T cells that 
      differentiates CpG DNA-mediated proliferation from survival and is required for 
      an in vivo T cell-dependent immune response.
FAU - Gelman, Andrew E
AU  - Gelman AE
AD  - Department of Medicine, University of Pennsylvania School of Medicine, 
      Philadelphia, PA 19010, USA.
FAU - LaRosa, David F
AU  - LaRosa DF
FAU - Zhang, Jidong
AU  - Zhang J
FAU - Walsh, Patrick T
AU  - Walsh PT
FAU - Choi, Yongwon
AU  - Choi Y
FAU - Sunyer, J Oriol
AU  - Sunyer JO
FAU - Turka, Laurence A
AU  - Turka LA
LA  - eng
GR  - R01 AI062789-01A1/AI/NIAID NIH HHS/United States
GR  - P01 AI041521/AI/NIAID NIH HHS/United States
GR  - AI-41521/AI/NIAID NIH HHS/United States
GR  - R01 AI062789/AI/NIAID NIH HHS/United States
GR  - AI-62789/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061019
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Interleukin-2)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cell Proliferation
MH  - CpG Islands/*immunology
MH  - Flow Cytometry
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Interleukin-2/immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloid Differentiation Factor 88/immunology/*metabolism
MH  - Phosphatidylinositol 3-Kinases/immunology/*metabolism
MH  - Signal Transduction/*immunology
PMC - PMC2840381
MID - NIHMS181519
EDAT- 2006/10/24 09:00
MHDA- 2006/12/23 09:00
PMCR- 2010/03/17
CRDT- 2006/10/24 09:00
PHST- 2006/02/15 00:00 [received]
PHST- 2006/07/11 00:00 [revised]
PHST- 2006/08/28 00:00 [accepted]
PHST- 2006/10/24 09:00 [pubmed]
PHST- 2006/12/23 09:00 [medline]
PHST- 2006/10/24 09:00 [entrez]
PHST- 2010/03/17 00:00 [pmc-release]
AID - S1074-7613(06)00442-0 [pii]
AID - 10.1016/j.immuni.2006.08.023 [doi]
PST - ppublish
SO  - Immunity. 2006 Nov;25(5):783-93. doi: 10.1016/j.immuni.2006.08.023. Epub 2006 Oct 
      19.