PMID- 14978090
OWN - NLM
STAT- MEDLINE
DCOM- 20040621
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 172
IP  - 5
DP  - 2004 Mar 1
TI  - A role for Toll-like receptor 4 in dendritic cell activation and cytolytic CD8+ T 
      cell differentiation in response to a recombinant heat shock fusion protein.
PG  - 2885-93
AB  - Recombinant heat shock fusion proteins (Hsfp) injected into mice without added 
      adjuvants can stimulate production of CD8 cytolytic T cells. Because initiation 
      of productive immune responses generally requires dendritic cell (DC) activation, 
      the question arises as to whether the Hsfp can activate DC independently of 
      contaminating LPS. Using microarray analyses of DC from LPS-insensitive mice 
      having a point mutation in Toll-like receptor 4 (Tlr4) (C3H/HeJ), or lacking Tlr4 
      (B10/ScNCr), we show here that unlike a LPS standard, Hsfp activated DC from HeJ 
      mice almost as well as DC from wild-type mice. Consistent with the microarray 
      analysis, the Hsfp's ability to activate DC was not eliminated by polymyxin B but 
      was destroyed by proteinase K. The Hsfp did not, however, stimulate DC from mice 
      lacking Tlr4. In vivo the CD8 T cell response to the Hsfp in mice lacking Tlr4 
      was impaired: the responding CD8 cells initially proliferated vigorously but 
      their development into cytolytic effector cells was diminished. Overall, the 
      results indicate that this Hsfp can activate DC independently of LPS but still 
      requires Tlr4 for an optimal CD8 T cell response.
FAU - Palliser, Deborah
AU  - Palliser D
AD  - Center for Cancer Research and Department of Biology, Massachusetts Institute of 
      Technology and the Whitehead Institute, Cambridge, MA 02139, USA.
FAU - Huang, Qian
AU  - Huang Q
FAU - Hacohen, Nir
AU  - Hacohen N
FAU - Lamontagne, Steven P
AU  - Lamontagne SP
FAU - Guillen, Eduardo
AU  - Guillen E
FAU - Young, Richard A
AU  - Young RA
FAU - Eisen, Herman N
AU  - Eisen HN
LA  - eng
GR  - AI-44477/AI/NIAID NIH HHS/United States
GR  - CA-14051/CA/NCI NIH HHS/United States
GR  - CA-60686/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Chaperonin 60)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (heat-shock protein 65, Mycobacterium)
RN  - EC 3.4.21.64 (Endopeptidase K)
RN  - EC 3.6.1.- (Chaperonins)
RN  - J2VZ07J96K (Polymyxin B)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/administration & dosage/*physiology
MH  - Cell Differentiation/immunology
MH  - Chaperonin 60
MH  - Chaperonins/administration & dosage/*physiology
MH  - Cytotoxicity, Immunologic/genetics
MH  - Dendritic Cells/drug effects/*immunology/*metabolism
MH  - Dose-Response Relationship, Immunologic
MH  - Endopeptidase K/pharmacology
MH  - Gene Expression Profiling
MH  - Lipopolysaccharides/administration & dosage
MH  - Lymphocyte Activation/genetics/immunology
MH  - Membrane Glycoproteins/deficiency/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polymyxin B/pharmacology
MH  - Receptors, Cell Surface/deficiency/genetics/*physiology
MH  - Recombinant Fusion Proteins/administration & dosage/*physiology
MH  - T-Lymphocytes, Cytotoxic/cytology/*immunology/*metabolism
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Up-Regulation/genetics/immunology
EDAT- 2004/02/24 05:00
MHDA- 2004/06/23 05:00
CRDT- 2004/02/24 05:00
PHST- 2004/02/24 05:00 [pubmed]
PHST- 2004/06/23 05:00 [medline]
PHST- 2004/02/24 05:00 [entrez]
AID - 10.4049/jimmunol.172.5.2885 [doi]
PST - ppublish
SO  - J Immunol. 2004 Mar 1;172(5):2885-93. doi: 10.4049/jimmunol.172.5.2885.