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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

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The IL-7/IL-7 receptor axis: understanding its central role in T-cell homeostasis and the challenges facing its

Sarah C Sasson1, John J Zaunders, Anthony D Kelleher

  • 1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. s.sasson@cfi.unsw.edu.au

Current Drug Targets
|December 16, 2006
PubMed

Interleukin-7 (IL-7) is a cytokine produced predominantly by stromal cells of the thymus and bone marrow and is essential for lymphopoiesis. This paper reviews the importance of IL-7 and its receptor (IL-7R) in T-cell genesis, peripheral survival, expansion and memory T-cell development. IL-7 is of particular importance in lymphopenic conditions. Its expression is up-regulated in a number of lymphopenic conditions including: marrow ablation prior to bone marrow transplantation, marrow suppression following chemotherapy and human immuno-deficiency virus (HIV) infection. Plasma IL-7 levels inversely correlate with CD4+ T-cell counts in these conditions. Animal models suggest that IL-7 improves immune reconstitution through increasing thymic output and, perhaps more importantly, through antigen-independent homeostatic driven proliferation in the periphery. Given the promising preliminary data on the use of IL-7 adjuvant therapy in simian immuno-deficiency virus (SIV) infected non-human primates, IL-7 has recently moved into Phase I/II clinical trials of its role as a possible adjuvant therapy for cancer and HIV infection. This paper discusses important considerations such as the possible negative impacts of IL-7 on increased viral infectivity, the induction of autoimmunity and risk of neoplastic events. Successful use of IL-7 will rely on further understanding of the regulation of the component parts of the IL-7R system. Ultimately this understanding may lead to therapeutics that manipulate and optimise signalling through the IL-7/IL-7R system.

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