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An IL-7 Fusion Protein That Shows Increased Thymopoietic Ability¹

Sian M. Henson^2,*, Robert Snelgrove, Tracy Hussell, Dominic J. Wells and Richard Aspinall^*

^* Department of Immunology, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom; Kennedy Institute, Imperial College, London, United Kingdom; and Gene Targeting Unit, Department of Cellular and Molecular Neuroscience, Imperial College, Charing Cross Hospital, London, United Kingdom

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.

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