PMID- 17237413
OWN - NLM
STAT- MEDLINE
DCOM- 20070327
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 3
DP  - 2007 Feb 1
TI  - Suppression of early IL-4 production underlies the failure of CD4 T cells 
      activated by TLR-stimulated dendritic cells to differentiate into Th2 cells.
PG  - 1635-44
AB  - Dendritic cells (DCs) activated through TLRs provide a potent negative signal for 
      Th2 cell development that is independent of positive signals for Th1 cell 
      development such as IL-12 and IFN-gamma. In this study we demonstrate that the 
      ability of TLR-activated DCs to suppress Th2 cell development is Ag 
      dose-independent and unique to DCs that have been activated through TLRs vs by 
      cytokines. We show that TLR-activated DCs inhibit early IL-4 production by CD4 T 
      cells and thus inhibit their ability to subsequently increase GATA-3 expression 
      and commit to the Th2 lineage. This occurs independently of expression of the 
      GATA-3 antagonist T-bet. Although CD4 T cells activated by TLR-activated DCs make 
      IL-2, they are not capable of phosphorylating STAT5 in response to this cytokine. 
      This inhibition of responsiveness to IL-2 appears to underlie the failure to make 
      early IL-4. Our findings suggest that DCs provide instructional signals for T 
      cell differentiation before cytokine-mediated Th cell selection and outgrowth.
FAU - Sun, Jie
AU  - Sun J
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Pearce, Edward J
AU  - Pearce EJ
LA  - eng
GR  - AI53825/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
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 (GATA3 Transcription Factor)
RN  - 0 (Gata3 protein, mouse)
RN  - 0 (Interleukin-2)
RN  - 0 (Toll-Like Receptors)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*cytology
MH  - Cell Differentiation/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - GATA3 Transcription Factor/genetics
MH  - Interleukin-2/*physiology
MH  - Interleukin-4/*biosynthesis
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Knockout
MH  - Th2 Cells/*cytology
MH  - Toll-Like Receptors/*physiology
MH  - Up-Regulation
EDAT- 2007/01/24 09:00
MHDA- 2007/03/28 09:00
CRDT- 2007/01/24 09:00
PHST- 2007/01/24 09:00 [pubmed]
PHST- 2007/03/28 09:00 [medline]
PHST- 2007/01/24 09:00 [entrez]
AID - 178/3/1635 [pii]
AID - 10.4049/jimmunol.178.3.1635 [doi]
PST - ppublish
SO  - J Immunol. 2007 Feb 1;178(3):1635-44. doi: 10.4049/jimmunol.178.3.1635.