Interleukin 7 (IL-7) is a type 1 short chain cytokine produced by the stromal cells of primary and secondary lymphoid organs which binds to a cell surface receptor composed of an IL-7 specific alpha chain (CD127) and a common gamma chain (CD132). The latter is termed common since it is used as one of the receptor chains for cytokines IL-2, 4, 9, 15 and 21 [
42]. Expression of CD127 and CD132 together are found at several stages of the T cell development pathway from early progenitors to memory cells. At the early intrathymic stages of the T cell pathway the IL-7:IL-7R interaction is responsible for ensuring cell survival [
43] may be responsible for generating T cell receptor diversity [
44] and is associated with clonal expansion of mature thymocytes prior to their export to the naïve T cell pool [
45]. In peripheral T cells the IL-7 ligand receptor interaction is mainly associated with clonal maintenance through ensuring cell survival and proliferation in both the naïve and memory T cell pools [
46]. The potential for IL-7 to act as an immune rejuvenating agent came from initial studies by Bhatia et al. [
47] on young mice treated for prolonged periods with anti-IL-7 antibody. These mice showed severe thymic atrophy and a decline in thymic cellularity similar to that seen in older animals. Treatment of old mice with IL-7 could reverse age-related atrophy of the thymus, leading to a restoration of thymic output and an improvement in peripheral T cell function [
43,
48]. One striking feature of using IL-7 to reverse thymic atrophy was the importance of the quantity of IL-7 present in the thymus as shown by experiments in which three lines of transgenic mice were generated in which the IL-7 gene was placed under the control of an lcx promoter. Each line produced different amounts of IL-7 and the line which produced the most (termed TgB) showed lower levels of thymocytes numbers when compared with wild type controls and were found to have a bottleneck in differentiation at the early stage of T cell development [
49]. Later work suggest that high levels of IL-7 antagonise Notch signalling and as such impact on the choice of T versus B cell lineage by stem cells in the thymus [
50]. Rejuvenation of immunity in old female rhesus macaques treated with recombinant simian IL-7 prior to vaccination with influenza showed an increase in thymic output and higher haemagglutinin titres in treated animals compared to saline treated controls [
51]. The first clinical trial using IL-7 examined the therapeutic effects of IL-7 administered to humans with metastatic cancer [
52]. A more recent placebo controlled double blind phase IIa trial in patients with lymphopaenic metastatic breast cancer [
53], some of whom received recombinant IL-7 as part of their treatment regimen reported encouraging results with IL-7 inducing a significant increase in T cell numbers when delivered before chemotherapy. In another study on HIV infected patients who were also receiving antiviral therapy the data suggest that repeated cycles of recombinant human IL-7 were tolerated quite well by the recipients and sustained T cell restoration was seen in the majority of the participants of the study [
53]. To date no trial has reported on the treatment of healthy older individuals who have received IL-7 therapy.