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Adenosine Generation Catalyzed By CD39 And CD73 Expressed On Regulatory T Cells Mediates Immune Suppression
S. Deaglio, K. Dwyer, Wenda Gao, D. Friedman, A. Usheva, Anna Erat, J. Chen, K. Enjyoji, J. Linden, M. Oukka, V. Kuchroo, T. Strom, S. Robson
Published 2007 · Biology, Medicine
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The study of T regulatory cells (T reg cells) has been limited by the lack of specific surface markers and an inability to define mechanisms of suppression. We show that the expression of CD39/ENTPD1 in concert with CD73/ecto-5′-nucleotidase distinguishes CD4+/CD25+/Foxp3+ T reg cells from other T cells. These ectoenzymes generate pericellular adenosine from extracellular nucleotides. The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. Consequently, T reg cells from Cd39-null mice show impaired suppressive properties in vitro and fail to block allograft rejection in vivo. We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation.
This paper references
Gene dose eff ect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene- defi cient mice
J M Armstrong (2001)
B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes.
B. Salomon (2000)
Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells.
Joachim C. U. Lehmann (2002)
Regulatory T cells, derived from naive CD4+CD25- T cells by in vitro Foxp3 gene transfer, can induce transplantation
J. G. Chai (2005)
Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion.
S. Huang (1997)
CD26, let it cut or cut it down.
I. De Meester (1999)
The role of CD4+ T‐cell subsets in determining transplantation rejection or tolerance
D. Zelenika (2001)
Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene-deficient mice.
J. M. Armstrong (2001)
Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage
A. Ohta (2001)
An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation
C. Asseman (1999)
Regulatory T cell lineage specification by the forkhead transcription factor foxp3.
J. Fontenot (2005)
T Regulatory and Primed Uncommitted CD4 T Cells Express CD73, Which Suppresses Effector CD4 T Cells by Converting 5′-Adenosine Monophosphate to Adenosine1
J. Kobie (2006)
Palmitoylation Targets CD39/Endothelial ATP Diphosphohydrolase to Caveolae*
K. Koziak (2000)
Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo
M. Chen (2005)
Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo.
M. Chen (2005)
Natural regulatory T cells in infectious disease
Y. Belkaid (2005)
Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease.
S. Paust (2004)
Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance.
X. Zheng (2003)
Cutting Edge: Critical Role for A2A Adenosine Receptors in the T Cell-Mediated Regulation of Colitis1
M. Naganuma (2006)
Foxp3-dependent programme of regulatory T-cell differentiation
M. Gavin (2007)
Unique Chemotactic Response Profile and Specific Expression of Chemokine Receptors Ccr4 and Ccr8 by Cd4+Cd25+ Regulatory T Cells
A. Iellem (2001)
Expression of the integrin αEβ7 identifies unique subsets of CD25+ as well as CD25− regulatory T cells
Joachim C. U. Lehmann (2002)
Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3
L. M. Williams (2007)
In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia.
S. Deaglio (2006)
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
E. Bettelli (2006)
A2A adenosine receptor protects tumors from antitumor T cells
A. Ohta (2006)
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
S. Sakaguchi (1995)
Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation
K. Enjyoji (1999)
Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo.
A. A. Erdmann (2005)
Regulatory Cells and Infectious Agents: Détentes Cordiale and Contraire
B. Rouse (2004)
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
S. Hori (2003)
The 'danger' sensors that STOP the immune response: the A2 adenosine receptors?
M. Sitkovsky (2005)
Ecto‐enzyme and signaling functions of lymphocyte CD 7 3
R. Resta (1998)
Ido expression by dendritic cells: tolerance and tryptophan catabolism
A. Mellor (2004)
Regulatory T cell lineage specifi cation by the forkhead transcription factor foxp3. Immunity. 22:329–341
J. D. Fontenot (2005)
Regulatory T Cells Key Controllers of Immunologic Self-Tolerance
S. Sakaguchi (2000)
Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation.
J. Sévigny (2002)
CD39 is the dominant Langerhans cell–associated ecto-NTPDase: Modulatory roles in inflammation and immune responsiveness
N. Mizumoto (2002)
Simulation of extracellular nucleotide hydrolysis and determination of kinetic constants for the ectonucleotidases.
L. L. Slakey (1986)
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
W. Liu (2006)
Gene dose eff ect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-genedefi cient mice
J. M. Armstrong (2001)
Regulatory T Cells, Derived from Naïve CD4+CD25− T Cells by In Vitro Foxp3 Gene Transfer, Can Induce Transplantation Tolerance
Jian-Guo Chai (2005)
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Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia.
H. Kang (2010)
Physical fitness modulates the expression of CD39 and CD73 on CD4+ CD25− and CD4+ CD25+ T cells following high intensity interval exercise
G. Dorneles (2019)
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M. Pettengill (2009)
The dark side of immunotherapy: pancreatic cancer
Gianluca Mucciolo (2020)
Targeting human inducible regulatory T cells (Tr1) in patients with cancer: blocking of adenosine–prostaglandin E2 cooperation
M. Mandapathil (2011)
In vitro generation of human FOXP3+ regulatory T cells
Ghusoon Abdulhameed Ebrahim Salman Abdulrasool (2014)
Natural CD4 + CD25 + FOXP3 + regulatory T cells in graft-versus-host disease
Matthias Edinger (2013)
AB0035 A physiological network of igg autoantibodies targeting g protein coupled receptors
O.C. Marques (2018)
CD 39 Expression Identifies Terminally Exhausted CD 8 + T Cells
Prakash K. Gupta (2015)
Control of inflammation, helper T cell responses and regulatory T cell function by Bcl6
Deepali V Sawant (2012)
Defining a Role for T Regulatory Cell Expressed MyD88 During the Response to Allografts
Christopher M. Borges (2015)
Regulation of lymphocyte function by adenosine.
J. Linden (2012)
Effectors and regulators of cellular immune response in autoimmune liver disease
R. Liberal (2012)
The Distribution of CD 8-and Foxp 3-positive T Cells in Skin Squamous Cell Tumors and Basal Cell Carcinomas
T. J. Jang (2015)
CD39 is a promising therapeutic antibody target for the treatment of soft tissue sarcoma.
G. M. Hayes (2015)
Improving stability of human regulatory T cells for clinical purposes
X. He (2016)
CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice.
L. Wang (2011)
Generation of anti‐inflammatory adenosine byleukocytes is regulated by TGF‐β
F. Regateiro (2011)
Homing‐associated molecules CD73 and VAP‐1 as targets to prevent harmful inflammations and cancer spread
M. Salmi (2011)
A Novel Cytomegalovirus-Induced Regulatory-Type T-Cell Subset Increases in Size During Older Life and Links Virus-Specific Immunity to Vascular Pathology
Nadia Terrazzini (2014)
The role of the IL23/IL17 pathway in inflammatory bowel disease
A. Geremia (2011)
Use of CFSE to Monitor Ex Vivo Regulatory T-cell Suppression of CD4+ and CD8+ T-cell Proliferation within Unseparated Mononuclear Cells from Malignant and Non-Malignant Human Lymph Node Biopsies
S. Hilchey (2007)
Effect of combined anti-PD-1 and temozolomide therapy in glioblastoma
J. Park (2019)
Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases
Xi Jia (2019)
Reduction in murine acute GVHD severity by human gingival tissue-derived mesenchymal stem cells via the CD39 pathways
X. Ni (2019)
The PI3K/AKT signaling pathway in regulatory T‐cell development, stability, and function
Saige L Pompura (2018)
Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis
L. M. S. Pereira (2017)
Thymic and Postthymic Regulation of Naïve CD4+ T-Cell Lineage Fates in Humans and Mice Models
J. Belizário (2016)
Changing perspective on oncometabolites: from metabolic signature of cancer to tumorigenic and immunosuppressive agents
M. Corrado (2016)
Importance of Regulatory T Cells in the Pathogenesis of Psoriasis: Review of the Literature
C. Mattozzi (2013)
Regulatory T cells: how do they suppress immune responses?
S. Sakaguchi (2009)
Streptococcus pneumoniae Serotype 1 Capsular Polysaccharide Induces CD8+CD28− Regulatory T Lymphocytes by TCR Crosslinking
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