PMID- 24420080
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20171116
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 44
IP  - 4
DP  - 2014 Apr
TI  - A CD40/CD40L feedback loop drives the breakdown of CD8(+) T-cell tolerance 
      following depletion of suppressive CD4(+) T cells.
PG  - 1099-107
LID - 10.1002/eji.201343738 [doi]
AB  - Dendritic cells (DCs) are the key APCs not only for the priming of naive T cells, 
      but also for the induction and maintenance of peripheral T-cell tolerance. We 
      have recently shown that cognate interactions between Foxp3(+) Tregs and 
      steady-state DCs are crucial to maintain the tolerogenic potential of DCs. Using 
      DIETER mice, which allow the induction of antigen presentation selectively on DCs 
      without altering their maturation status, we show here that breakdown of CD8(+) 
      T-cell tolerance, which ensues after depletion of suppressive CD4(+) T cells, is 
      driven by a positive feedback loop in which autoreactive CD8(+) T cells activate 
      DCs via CD40. These data identify ligation of CD40 on DCs as a stimulus that 
      promotes autoreactive T-cell priming when regulatory T-cell suppression fails and 
      suggest that feedback from autoreactive T cells to DCs may contribute to the 
      well-documented involvement of CD40 in many autoimmune diseases.
CI  - (c) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Muth, Sabine
AU  - Muth S
AD  - Institute for Immunology, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany; Research Center for Immunology (FZI), Mainz, 
      Germany.
FAU - Schutze, Kristian
AU  - Schutze K
FAU - Hain, Tobias
AU  - Hain T
FAU - Yagita, Hideo
AU  - Yagita H
FAU - Schild, Hansjorg
AU  - Schild H
FAU - Probst, Hans Christian
AU  - Probst HC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140120
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD40 Antigens)
RN  - 0 (monoclonal antibody GK1.5)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigen Presentation/immunology
MH  - Bone Marrow Transplantation
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism
MH  - CD40 Antigens/genetics/*immunology/metabolism
MH  - CD40 Ligand/genetics/*immunology/metabolism
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cell Line, Tumor
MH  - Dendritic Cells/immunology/metabolism
MH  - Feedback, Physiological/drug effects
MH  - Flow Cytometry
MH  - Immune Tolerance/genetics/*immunology
MH  - Lymphocytic Choriomeningitis/immunology/virology
MH  - Lymphocytic choriomeningitis virus/immunology/physiology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - T-Lymphocytes, Cytotoxic/immunology/metabolism
MH  - Transplantation Chimera/blood/immunology
OTO - NOTNLM
OT  - CD40 ligation
OT  - CD8+ T cells
OT  - Dendritic cells
OT  - Peripheral tolerance
EDAT- 2014/01/15 06:00
MHDA- 2014/06/24 06:00
CRDT- 2014/01/15 06:00
PHST- 2013/05/24 00:00 [received]
PHST- 2013/11/21 00:00 [revised]
PHST- 2013/12/12 00:00 [accepted]
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
AID - 10.1002/eji.201343738 [doi]
PST - ppublish
SO  - Eur J Immunol. 2014 Apr;44(4):1099-107. doi: 10.1002/eji.201343738. Epub 2014 Jan 
      20.