title: An IL-7 fusion protein that shows increased thymopoietic ability.
abstract: The role of IL-7 during thymopoiesis has led to it being the focus of a number of therapeutic interventions. However, its small size and pleiotropic nature present problems for thymus-directed therapies. We have created a fusion molecule between the extracellular N-terminal domain of CCR9 and IL-7, which has the potential to overcome these difficulties. This novel fusion protein retains the thymopoietic activity of IL-7 and the ligand-binding ability of CCR9. As a thymopoietic agent, compared with IL-7, it shows an enhanced retention in the thymus, increased de novo T cell production, and increased thymic output. Old mice receiving the fusion protein show improved CD8 T cell responses and reduced viral load after infection with influenza virus compared with those receiving IL-7. This chimeric molecule offers a novel therapeutic strategy that may result in the production of an effective immunorestorative agent.
authors.affiliation: Department of Immunology, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom. s.henson@ucl.ac.uk
authors.forename: Sian M
authors.initials: SM
authors.lastname: Henson
authors.forename: Robert
authors.initials: R
authors.lastname: Snelgrove
authors.forename: Tracy
authors.initials: T
authors.lastname: Hussell
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Wells
authors.forename: Richard
authors.initials: R
authors.lastname: Aspinall
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D015202:Protein Engineering; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology; D019562:Viral Load
chemical_list: C119309:CC chemokine receptor 9; D015851:Interleukin-7; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins