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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1162-1169.
Prepublished online as a Blood First Edition Paper on October 12, 2004; DOI 10.1182/blood-2004-03-1211.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells
Megan K. Levings,
Silvia Gregori,
Eleonora Tresoldi,
Sabrina Cazzaniga,
Chiara Bonini, and
Maria Grazia Roncarolo
From the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET); Cancer Immunotherapy and Gene Therapy Program, San Raffaele Scientific Institute; and Università Vita-Salute San Raffaele Milan, Italy.
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  (TGF-)–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.
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|
|
|
|
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|
|
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180(8):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Atanackovic, N. K. Altorki, Y. Cao, E. Ritter, C. A. Ferrara, G. Ritter, E. W. Hoffman, C. Bokemeyer, L. J. Old, and S. Gnjatic
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105(5):
1650 - 1655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mariotti, J. Foley, U. Jung, T. Borenstein, N. Kantardzic, S. Han, J. T. Hanson, E. Wong, N. Buxhoeveden, J. B. Trepel, et al.
Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection
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180(1):
89 - 105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wang, M. Toda, K. Saito, T. Hori, T. Horii, H. Shiku, K. Kuribayashi, and T. Kato
Post-immune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses
Int. Immunol.,
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20(1):
57 - 70.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yamazaki, A. J. Bonito, R. Spisek, M. Dhodapkar, K. Inaba, and R. M. Steinman
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110(13):
4293 - 4302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Cools, P. Ponsaerts, V. F. I. Van Tendeloo, and Z. N. Berneman
Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells
J. Leukoc. Biol.,
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82(6):
1365 - 1374.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Balkow, F. Krux, K. Loser, J. U. Becker, S. Grabbe, and U. Dittmer
Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naive T cells, and favors expansion of regulatory T cells
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110(12):
3949 - 3958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Naji, S. Le Rond, A. Durrbach, I. Krawice-Radanne, C. Creput, M. Daouya, J. Caumartin, J. LeMaoult, E. D. Carosella, and N. Rouas-Freiss
CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance
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110(12):
3936 - 3948.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Molitor-Dart, J. Andrassy, J. Kwun, H. A. Kayaoglu, D. A. Roenneburg, L. D. Haynes, J. R. Torrealba, J. L. Bobadilla, H. W. Sollinger, S. J. Knechtle, et al.
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J. Immunol.,
November 15, 2007;
179(10):
6749 - 6761.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bergmann, L. Strauss, R. Zeidler, S. Lang, and T. L. Whiteside
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September 15, 2007;
67(18):
8865 - 8873.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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Both Infiltrating Regulatory T Cells and Insufficient Antigen Presentation Are Involved in Long-Term Cardiac Xenograft Survival
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August 1, 2007;
179(3):
1542 - 1548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Feger, E. Tolosa, Y.-H. Huang, A. Waschbisch, T. Biedermann, A. Melms, and H. Wiendl
HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation
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July 15, 2007;
110(2):
568 - 577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper
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July 1, 2007;
110(1):
211 - 219.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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J. Exp. Med.,
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204(5):
1037 - 1047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. M. den Haan, G. Kraal, and M. J. Bevan
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J. Immunol.,
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178(9):
5429 - 5433.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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13(7):
2075 - 2081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Anderson, M. Oukka, V. J. Kuchroo, and D. Sacks
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J. Exp. Med.,
February 19, 2007;
204(2):
285 - 297.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Jankovic, M. C. Kullberg, C. G. Feng, R. S. Goldszmid, C. M. Collazo, M. Wilson, T. A. Wynn, M. Kamanaka, R. A. Flavell, and A. Sher
Conventional T-bet+Foxp3- Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection
J. Exp. Med.,
February 19, 2007;
204(2):
273 - 283.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ito, M. Yang, Y.-H. Wang, R. Lande, J. Gregorio, O. A Perng, X.-F. Qin, Y.-J. Liu, and M. Gilliet
Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand
J. Exp. Med.,
January 22, 2007;
204(1):
105 - 115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Cabbage, E. S. Huseby, B. D. Sather, T. Brabb, D. Liggitt, and J. Goverman
Regulatory T Cells Maintain Long-Term Tolerance to Myelin Basic Protein by Inducing a Novel, Dynamic State of T Cell Tolerance
J. Immunol.,
January 15, 2007;
178(2):
887 - 896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Y. Lan, Z. Wang, G. Raimondi, W. Wu, B. L. Colvin, A. De Creus, and A. W. Thomson
"Alternatively Activated" Dendritic Cells Preferentially Secrete IL-10, Expand Foxp3+CD4+ T Cells, and Induce Long-Term Organ Allograft Survival in Combination with CTLA4-Ig
J. Immunol.,
November 1, 2006;
177(9):
5868 - 5877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bharat, R. C. Fields, E. P. Trulock, G. A. Patterson, and T. Mohanakumar
Induction of IL-10 Suppressors in Lung Transplant Patients by CD4+25+ Regulatory T Cells through CTLA-4 Signaling
J. Immunol.,
October 15, 2006;
177(8):
5631 - 5638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Grimbert, S. Bouguermouh, N. Baba, T. Nakajima, Z. Allakhverdi, D. Braun, H. Saito, M. Rubio, G. Delespesse, and M. Sarfati
Thrombospondin/CD47 Interaction: A Pathway to Generate Regulatory T Cells from Human CD4+CD25- T Cells in Response to Inflammation
J. Immunol.,
September 15, 2006;
177(6):
3534 - 3541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Ding, L. Lu, B. Wang, Y. Zhou, Y. Jiang, X. Zhou, L. Xin, Z. Jiao, and K.-Y. Chou
B7H1-Ig Fusion Protein Activates the CD4+ IFN-{gamma} Receptor+ Type 1 T Regulatory Subset through IFN-{gamma}-Secreting Th1 Cells
J. Immunol.,
September 15, 2006;
177(6):
3606 - 3614.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ito, Y.-H. Wang, O. Duramad, S. Hanabuchi, O. A. Perng, M. Gilliet, F. X.-F. Qin, and Y.-J. Liu
OX40 ligand shuts down IL-10-producing regulatory T cells
PNAS,
August 29, 2006;
103(35):
13138 - 13143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hoves, S. W. Krause, C. Schutz, D. Halbritter, J. Scholmerich, H. Herfarth, and M. Fleck
Monocyte-Derived Human Macrophages Mediate Anergy in Allogeneic T Cells and Induce Regulatory T Cells
J. Immunol.,
August 15, 2006;
177(4):
2691 - 2698.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Rutella, G. Bonanno, A. Procoli, A. Mariotti, D. G. de Ritis, A. Curti, S. Danese, G. Pessina, S. Pandolfi, F. Natoni, et al.
Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features
Blood,
July 1, 2006;
108(1):
218 - 227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. D. Mennechet and G. Uze
Interferon-{lambda}-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells
Blood,
June 1, 2006;
107(11):
4417 - 4423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kim-Schulze, L. Scotto, G. Vlad, F. Piazza, H. Lin, Z. Liu, R. Cortesini, and N. Suciu-Foca
Recombinant Ig-Like Transcript 3-Fc Modulates T Cell Responses via Induction of Th Anergy and Differentiation of CD8+ T Suppressor Cells.
J. Immunol.,
March 1, 2006;
176(5):
2790 - 2798.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Veldman, A. Pahl, S. Beissert, W. Hansen, J. Buer, D. Dieckmann, G. Schuler, and M. Hertl
Inhibition of the transcription factor foxp3 converts desmoglein 3-specific type 1 regulatory T cells into th2-like cells.
J. Immunol.,
March 1, 2006;
176(5):
3215 - 3222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yamazaki, M. Patel, A. Harper, A. Bonito, H. Fukuyama, M. Pack, K. V. Tarbell, M. Talmor, J. V. Ravetch, K. Inaba, et al.
Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction
PNAS,
February 21, 2006;
103(8):
2758 - 2763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Li, J. Li, D. L. J. Tyrrell, and B. Agrawal
Expression of hepatitis C virus-derived core or NS3 antigens in human dendritic cells leads to induction of pro-inflammatory cytokines and normal T-cell stimulation capabilities
J. Gen. Virol.,
January 1, 2006;
87(1):
61 - 72.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. K. Crellin, R. V. Garcia, O. Hadisfar, S. E. Allan, T. S. Steiner, and M. K. Levings
Human CD4+ T Cells Express TLR5 and Its Ligand Flagellin Enhances the Suppressive Capacity and Expression of FOXP3 in CD4+CD25+ T Regulatory Cells
J. Immunol.,
December 15, 2005;
175(12):
8051 - 8059.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Delgado, E. Gonzalez-Rey, and D. Ganea
The Neuropeptide Vasoactive Intestinal Peptide Generates Tolerogenic Dendritic Cells
J. Immunol.,
December 1, 2005;
175(11):
7311 - 7324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Chorny, E. Gonzalez-Rey, A. Fernandez-Martin, D. Pozo, D. Ganea, and M. Delgado
Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders
PNAS,
September 20, 2005;
102(38):
13562 - 13567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Chauveau, S. Remy, P. J. Royer, M. Hill, S. Tanguy-Royer, F.-X. Hubert, L. Tesson, R. Brion, G. Beriou, M. Gregoire, et al.
Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression
Blood,
September 1, 2005;
106(5):
1694 - 1702.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Vlad, R. Cortesini, and N. Suciu-Foca
License to Heal: Bidirectional Interaction of Antigen-Specific Regulatory T Cells and Tolerogenic APC
J. Immunol.,
May 15, 2005;
174(10):
5907 - 5914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Y. Wan and R. A. Flavell
Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter
PNAS,
April 5, 2005;
102(14):
5126 - 5131.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
