Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression

By S. Deaglio, K. Dwyer, Wenda Gao, D. Friedman, A. Usheva, Anna Erat, Jiang-fan Chen, K. Enjyoji, J. Linden, M. Oukka and 3 more. Journal of Experimental Medicine, 2007

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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.

Subfields: Epidemiology, Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/4e52cbfa242d4335378ba90d8924f312084e2de8

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In Physiology

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Citations in the corpus

• The blockade of immune checkpoints in cancer immunotherapy (2012, background): “In addition, T Reg cells express high levels of the exoenzymes CD39 (also known as NTPDase 1), which converts extracellular ATP to AMP, and CD73 (also known as 5′-NT), which converts AMP to adenosin”
• CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation–mediated apoptosis of effector CD4+ T cells (2007, background): “It will be useful to precisely delineate how adenosine receptor”
• Mechanisms of foxp3+ T regulatory cell-mediated suppression. (2009, background): “Adenosine can be generated by CD39 in concert with the 50- ecto-nucleoside CD73, which dephosphorylates the CD39 product, AMP (Deaglio et al., 2007).”
• Regulatory T cells: how do they suppress immune responses? (2009, background): “... contact, Tregs may kill responder T cells by a granzyme-dependent or perforin-dependent mechanism (17, 18) or deliver a negative signal to responder T cells via (i) up-regulating intracellular cyclic AMP, which leads to inhibition of T cell proliferation and IL-2 formation (19); (ii) generating ”