title: CD73 is dispensable for the regulation of inflationary CD8+ T-cells after murine cytomegalovirus infection and adenovirus immunisation.
abstract: The ecto-5'-nucleotidase (CD73) is expressed by T-cell subsets, myeloid derived suppressive cells and endothelial cells. It works in conjunction with CD39 to regulate the formation and degradation of adenosine in vivo. Adenosine has previously been shown to suppress the proliferation and cytokine secretion of T-cells and recent evidence suggests that inhibition of CD73 has the potential to enhance T-cell directed therapies. Here we utilised a CD73 knockout mouse model to assess the suppressive ability of CD73 on CD8+ T-cell classical memory and memory "inflation", induced by murine cytomegalovirus (MCMV) infection and adenovirus immunisation. We show that CD73 is dispensable for normal CD8+ T-cell differentiation and function in both models. Thus CD73 as a suppressor of CD8+ T-cells is unlikely to play a deterministic role in the generation and functional characteristics of antiviral memory in these settings.
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Sims
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Colston
authors.affiliation: Department of Biomedicine, University of Basel, Hebelstrasse 20, 4056 Basel
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bolinger
authors.affiliation: Department of Microbial and Cellular Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
authors.forename: Vince
authors.initials: V
authors.lastname: Emery
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D015720:5'-Nucleotidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control; D007114:Immunization; D051379:Mice; D018146:Muromegalovirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D010641:Phenotype; D013045:Species Specificity; D019562:Viral Load
chemical_list: D015720:5'-Nucleotidase