The IL-7/IL-7 receptor axis: understanding its central role in T-cell homeostasis and the challenges facing its utilization as a novel therapy.
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.
Sasson
Sarah C
SC
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. s.sasson@cfi.unsw.edu.au
Zaunders
John J
JJ
Kelleher
Anthony D
AD
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006410:Hematopoiesis; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000502:physiology* / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D020395:Receptors, Interleukin-7 / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D019380:Anti-HIV Agents; D015851:Interleukin-7; D020395:Receptors, Interleukin-7