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: Sian M Henson, Robert Snelgrove, Tracy Hussell, Dominic J Wells, Richard Aspinall
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 6 Pg. 4112-8 (Sep 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16148161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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