| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
David H. Smith Center for Vaccine Biology and Immunology and Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642
CD73 (5'-ectonucleotidase) is expressed by two distinct mouse CD4 T cell populations: CD25+ (FoxP3+) T regulatory (Treg) cells that suppress T cell proliferation but do not secrete IL-2, and CD25– uncommitted primed precursor Th (Thpp) cells that secrete IL-2 but do not suppress in standard Treg suppressor assays. CD73 on both Treg and Thpp cells converted extracellular 5'-AMP to adenosine. Adenosine suppressed proliferation and cytokine secretion of Th1 and Th2 effector cells, even when target cells were activated by anti-CD3 and anti-CD28. This represents an additional suppressive mechanism of Treg cells and a previously unrecognized suppressive activity of Thpp cells. Infiltration of either Treg or Thpp cells at inflammatory sites could potentially convert 5'-AMP generated by neutrophils or dying cells into the anti-inflammatory mediator adenosine, thus dampening excessive immune reactions.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants RO1 AI48604 and T32 CA09363-22 (to J.J.K.).
2 Address correspondence and reprint requests to Dr. Tim R. Mosmann, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 609, Rochester, NY 14642. E-mail address: Tim_Mosmann{at}urmc.rochester.edu
3 Abbreviations used in this paper: Thpp, primed precursor Th cells; APCP, 
,β-methylene ADP.
This article has been cited by other articles:
|
|
 |
|
  S. P. Hilchey, J. J. Kobie, M. R. Cochran, S. Secor-Socha, J.-C. E. Wang, O. Hyrien, W. R. Burack, T. R. Mosmann, S. A. Quataert, and S. H. Bernstein Human Follicular Lymphoma CD39+-Infiltrating T Cells Contribute to Adenosine-Mediated T Cell Hyporesponsiveness J. Immunol., November 15, 2009; 183(10): 6157 - 6166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ohta, A. Ohta, M. Madasu, R. Kini, M. Subramanian, N. Goel, and M. Sitkovsky A2A Adenosine Receptor May Allow Expansion of T Cells Lacking Effector Functions in Extracellular Adenosine-Rich Microenvironments J. Immunol., November 1, 2009; 183(9): 5487 - 5493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mandapathil, M. J. Szczepanski, M. Szajnik, J. Ren, D. E. Lenzner, E. K. Jackson, E. Gorelik, S. Lang, J. T. Johnson, and T. L. Whiteside Increased Ectonucleotidase Expression and Activity in Regulatory T Cells of Patients with Head and Neck Cancer Clin. Cancer Res., October 15, 2009; 15(20): 6348 - 6357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Kinsey, R. Sharma, L. Huang, L. Li, A. L. Vergis, H. Ye, S.-T. Ju, and M. D. Okusa Regulatory T Cells Suppress Innate Immunity in Kidney Ischemia-Reperfusion Injury J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1744 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-F. Lu and A. Rudensky Molecular orchestration of differentiation and function of regulatory T cells Genes & Dev., June 1, 2009; 23(11): 1270 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Wilson, W. G. Ross, O. N. Agbai, R. Frazier, R. A. Figler, J. Rieger, J. Linden, and P. B. Ernst The A2B Adenosine Receptor Impairs the Maturation and Immunogenicity of Dendritic Cells J. Immunol., April 15, 2009; 182(8): 4616 - 4623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bopp, N. Dehzad, S. Reuter, M. Klein, N. Ullrich, M. Stassen, H. Schild, R. Buhl, E. Schmitt, and C. Taube Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression J. Immunol., April 1, 2009; 182(7): 4017 - 4024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jeffe, K. A. Stegmann, F. Broelsch, M. P. Manns, M. Cornberg, and H. Wedemeyer Adenosine and IFN-{alpha} synergistically increase IFN-{gamma} production of human NK cells J. Leukoc. Biol., March 1, 2009; 85(3): 452 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Csoka, L. Himer, Z. Selmeczy, E. S. Vizi, P. Pacher, C. Ledent, E. A. Deitch, Z. Spolarics, Z. H. Nemeth, and G. Hasko Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function FASEB J, October 1, 2008; 22(10): 3491 - 3499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Sitkovsky, J. Kjaergaard, D. Lukashev, and A. Ohta Hypoxia-Adenosinergic Immunosuppression: Tumor Protection by T Regulatory Cells and Cancerous Tissue Hypoxia Clin. Cancer Res., October 1, 2008; 14(19): 5947 - 5952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Liston, L.-F. Lu, D. O'Carroll, A. Tarakhovsky, and A. Y. Rudensky Dicer-dependent microRNA pathway safeguards regulatory T cell function J. Exp. Med., September 1, 2008; 205(9): 1993 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Mills, L. F. Thompson, C. Mueller, A. T. Waickman, S. Jalkanen, J. Niemela, L. Airas, and M. S. Bynoe CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis PNAS, July 8, 2008; 105(27): 9325 - 9330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Winstead, J. M. Fraser, and A. Khoruts Regulatory CD4+CD25+Foxp3+ T Cells Selectively Inhibit the Spontaneous Form of Lymphopenia-Induced Proliferation of Naive T Cells J. Immunol., June 1, 2008; 180(11): 7305 - 7317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takedachi, D. Qu, Y. Ebisuno, H. Oohara, M. L. Joachims, S. T. McGee, E. Maeda, R. P. McEver, T. Tanaka, M. Miyasaka, et al. CD73-Generated Adenosine Restricts Lymphocyte Migration into Draining Lymph Nodes J. Immunol., May 1, 2008; 180(9): 6288 - 6296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jalkanen and M. Salmi VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 18 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Borsellino, M. Kleinewietfeld, D. Di Mitri, A. Sternjak, A. Diamantini, R. Giometto, S. Hopner, D. Centonze, G. Bernardi, M. L. Dell'Acqua, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression Blood, August 15, 2007; 110(4): 1225 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Deaglio, K. M. Dwyer, W. Gao, D. Friedman, A. Usheva, A. Erat, J.-F. Chen, K. Enjyoji, J. Linden, M. Oukka, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression J. Exp. Med., June 11, 2007; 204(6): 1257 - 1265. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
