Thymus Function in AGHD Figure 2. Relationship between age and sjTREC frequency in PBMCs from patients with AGHD. A. Under GH treatment (R = 20.35, P = 0.11). B. One month after GH withdrawal (R = 20.5, P = 0.02). C. One month after GH resumption (R = 20.55, P,0.01). doi:10.1371/journal.pone.0005668.g002 Figure 3. Blood DbTREC frequency and sj/b TREC ratio. No significant modification was detected in blood DbTREC frequency after 1-month interruption of GH treatment, nor 1 month after GH resumption (A). The sj/b TREC ratio significantly declined after 1-month interruption of GH treatment. It was increased 1 month after GH- resumption but did not reach the level measured before the arrest of GH treatment. Results are shown as median with interquartiles. ** P,0.01 (by Wilcoxon’s signed rank test, N = 19). doi:10.1371/journal.pone.0005668.g003 Human thymic epithelial cells (TEC) predominantly express IGF- 2 and IGFBP-2 to -6 [32,33], while IGF-1 expression is restricted to scattered cells with a macrophage-like morphology and distribution [32,34]. Several lines of evidence also argue for IGF-1 expression by human TEC [35]. Human thymocytes express type 1 IGF receptor (IGF-1R) [36], and IGF-1 administration stimulates repopulation of the atrophic thymus in diabetic rats [37]. IGF-1 also regenerates the thymus in a rat model of dexamethasone-induced thymic atrophy [38]. Further- more, in murine fetal thymic organ cultures (FTOC), the treatment with anti-IGF-1R decreased the total T cell number by 81%, whereas murine FTOC treated with anti-M6P/IGF-2R PLoS ONE | www.plosone.org 5 May 2009 | Volume 4 | Issue 5 | e5668