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.

Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

“…Previous studies have shown that IL-7 therapy stimulates thymopoiesis and thereby increases the output of naive T cells from the thymus (36). Here, we sought to determine whether the enhancement of CD8 T cell memory by IL-7 ( Figure 4) is independent of increased output of naive CD8 T cells from the thymus.…”

Central Immune Senescence, Reversal Potentials

“…An example is the thymus-specific enrichment of transgenic IL7 proteins using IL7-CCR9 fusion proteins that selectively home and accumulate in the thymic context to reinforce thymocyte development and maturation (Henson et al 2005). This method has been characterised in detail and is currently being geared up towards potential human application in the form of inhalation products selectively delivering IL7 to the thymus (Aspinall et al 2008).…”

Reversing T cell immunosenescence: why, who, and how

“…As previously mentioned, it plays a pivotal role in supporting thymocytes development, as well as peripheral T cells survival and proliferation (Kim et al 1998;Jiang et al 2005). Some studies carried out in old animals have reported that IL-7 reversed thymic atrophy, increased thymopoiesis improved thymic output, and boosting immune function (Aspinall and Andrew 2001;Henson et al 2005;Pellegrini et al 2011). Thus, old female rhesus macaques injected with recombinant IL-7 subcutaneously (60 g/kg) for a 14-day period, compared to animals receiving saline vehicle alone, showed an increase not only in the number of CD4 +…”