An IL-7 fusion protein that shows increased thymopoietic ability

J Immunol. 2005 Sep 15;175(6):4112-8. doi: 10.4049/jimmunol.175.6.4112.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation / drug effects
  • Influenza, Human / drug therapy
  • Influenza, Human / immunology
  • Interleukin-7 / genetics
  • Interleukin-7 / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Protein Engineering
  • Receptors, CCR
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / therapeutic use
  • Recombinant Fusion Proteins / therapeutic use
  • T-Lymphocytes / drug effects*
  • Thymus Gland / drug effects*
  • Thymus Gland / immunology
  • Viral Load

Substances

  • CC chemokine receptor 9
  • Interleukin-7
  • Receptors, CCR
  • Receptors, Chemokine
  • Recombinant Fusion Proteins