title: Roles of the adenosine receptor and CD73 in the regulatory effect of γδ T cells.
abstract: The adenosine A2A receptor (A2AR), the main functional adenosine receptor on murine T cells, plays a unique role in the attenuation of inflammation and tissue damage in vivo. Here, we showed that, of the immune cell types tested, activated γδ T cells expressed the highest levels of A2AR mRNA and that A2AR ligation inhibited αβ T cell activation, but enhanced γδ T cell activation. We also showed that the inhibitory effect of an adenosine receptor agonist on autoreactive T cells was prevented by addition of a low percentage of activated γδ T cells. Furthermore, compared to resting cells, activated γδ T cells expressed significantly lower levels of CD73, an enzyme involved in the generation of extracellular adenosine. Exogenous AMP had a significant inhibitory effect on autoreactive T cell responses, but only in the presence of CD73+ γδ T cells, and this effect was abolished by a CD73 inhibitor. Our results show that expression of increased amounts of A2AR allows γδ T cells to bind adenosine and thereby attenuate its suppressive effect, while decreased expression of CD73 results in less generation of adenosine in the inflammatory site. Together, these events allow activated γδ T cells to acquire increased proinflammatory activity, leading to augmented autoimmune responses.
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zuo
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Mingjiazi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010627:Phenethylamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D016207:Cytokines; D015226:Dinucleoside Phosphates; D010627:Phenethylamines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C083343:adenylyl(3'-5')cytidine-3'-phosphate; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D000241:Adenosine