PMID- 15479730
OWN - NLM
STAT- MEDLINE
DCOM- 20050421
LR  - 20220129
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 3
DP  - 2005 Feb 1
TI  - Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not 
      CD25+CD4+ Tr cells.
PG  - 1162-9
AB  - Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the 
      antigenic environment and activate naive T cells. The role of DCs is not only to 
      sense danger but also to tolerize the immune system to antigens encountered in 
      the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell 
      encounters its antigen on immature DCs (iDCs), it may differentiate into a 
      T-regulatory (Tr) rather than a T-effector cell. However, little is known about 
      the mechanisms by which iDCs differentiate Tr cells. We developed a standardized 
      and highly reproducible protocol to differentiate Tr cells by repetitive exposure 
      of naive peripheral blood CD4(+) T cells to allogeneic iDCs. The resultant Tr 
      cells are phenotypically and functionally identical to type 1 Tr (Tr1) cells 
      because their generation requires production of IL-10 by iDCs, and they suppress 
      T-cell responses through an interleukin-10 (IL-10)- and a transforming growth 
      factor beta (TGF-beta)-dependent mechanism. In addition, Tr1 cells induced by 
      iDCs do not require the presence of CD4(+)CD25(+) Tr cells for their generation, 
      nor do they express high constitutive levels of CD25 or the transcription factor 
      FoxP3. Thus, iDCs can drive the differentiation of Tr1 cells and can be used to 
      generate large numbers of alloantigen-specific Tr1 cells for clinical use as a 
      cellular therapy to restore peripheral tolerance.
FAU - Levings, Megan K
AU  - Levings MK
AD  - San Rafaele Telethon Institute for Gene Therapy, Via Olgettina 58, Milan, Italy.
FAU - Gregori, Silvia
AU  - Gregori S
FAU - Tresoldi, Eleonora
AU  - Tresoldi E
FAU - Cazzaniga, Sabrina
AU  - Cazzaniga S
FAU - Bonini, Chiara
AU  - Bonini C
FAU - Roncarolo, Maria Grazia
AU  - Roncarolo MG
LA  - eng
GR  - TGT03F01/TI_/Telethon/Italy
GR  - TGT06S01/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041012
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CD4 Antigens)
RN  - 0 (Receptors, Interleukin-2)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - CD4 Antigens/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Differentiation/drug effects/immunology
MH  - Cell Division
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Interleukin-10/*pharmacology
MH  - Lymphocyte Activation/*immunology
MH  - Receptors, Interleukin-2/immunology
MH  - Reference Values
MH  - T-Lymphocytes/cytology/drug effects/*immunology
EDAT- 2004/10/14 09:00
MHDA- 2005/04/22 09:00
CRDT- 2004/10/14 09:00
PHST- 2004/10/14 09:00 [pubmed]
PHST- 2005/04/22 09:00 [medline]
PHST- 2004/10/14 09:00 [entrez]
AID - S0006-4971(20)46807-7 [pii]
AID - 10.1182/blood-2004-03-1211 [doi]
PST - ppublish
SO  - Blood. 2005 Feb 1;105(3):1162-9. doi: 10.1182/blood-2004-03-1211. Epub 2004 Oct 
      12.