Adenosine produced by a CD38-mediated pathway in CD56bright CD16- NK cells inhibits autologous CD4+T cell proliferation
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1
Istituto Giannina Gaslini, Italy
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2
University of Torino, Department of Medical Sciences, Italy
Recent studies have indicated that CD56brightCD16- natural killer (NK) cells play an important role in immunoregulation and autoimmunity by mechanisms that have yet to be elucidated. In this study, we investigated the potential role of an extracellular nucleotide-metabolizing network that leads to production of adenosine (ADO), a multifunctional immunosuppressive nucleoside that binds to different specific receptors expressed by immune effector cells. The nucleotide-metabolizing ectoenzyme network includes the ADP-ribosyl cyclases CD38 and CD157, PC-1 [nucleotide pyrophosphatase/phosphodiesterase-1(ENPP-1)], CD39 (nucleoside triphosphate diphosphohydrolase-1) and CD73 (5’-nucleotidase). These ectoenzymes regulate the nucleotide/nucleoside balance and control the release of adenosine into the extracellular environment. We detected similar expression levels of CD38, CD39, CD73 and CD157 in peripheral blood CD56dim/CD16+ and CD56bright/CD16- NK cells, whereas PC-1 was mostly expressed in CD56dim/CD16+ cells. CD56bright/CD16- NK cells produced ADO when cultured in the presence of ATP, ADP (in progress), AMP or NAD+. ADO inhibited the proliferation of autologous CD4+ T cells. Pre-treatment with dipyridamole, which increases extracellular ADO by blocking ADO transporters, further inhibited CD4+ T cell proliferation. On the contrary, ADO-mediated inhibition of autologous CD4+ T cell proliferation was abrogated by blocking CD38 activity, but not by inhibiting CD39, CD73 or PC-1. These studies indicate that CD56bright/CD16- NK cells can mediate immune regulation through ADO production, a process that requires the ADP-ribosyl cyclase CD38.
Keywords:
NK cells,
Adenosine,
CD56bright,
Immunoregulation,
CD38/ADP-ribosyl cyclase activity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Morandi
F,
Horenstein
A,
Chillemi
A,
Zaccarello
G,
Malavasi
F and
Pistoia
V
(2013). Adenosine produced by a CD38-mediated pathway in CD56bright CD16- NK cells inhibits autologous CD4+T cell proliferation.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00867
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Received:
19 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Fabio Morandi, Istituto Giannina Gaslini, Genoa, Italy, fabiomorandi@gaslini.org