A – Signaling pathways linked to the intracellular domains of the IL-2Rβ and the γc chains based on Gaffen SL  and Leonard WJ and O'Shea . Highlighted boxes refer to different domains of the receptor subunits. Red arrows refer to pathways that appeared activated by rIL-2 administration and red gene names refer to those significantly up-regulated by rIL-2. Blue arrows and names refer respectively to pathways and genes whose expression was not affected by rIL-2. In green are pathways and genes significantly down regulated by rIL-2. The letters "s", "a" and "h" refer to the proximal, middle and distal regions of the IL-2Rβ chain – B Relative expression of various genes associated with IL-2R signaling whose expression is significantly affected by rIL-2 based on a two-tailed paired t test comparing non-stimulated with rIL-2-stiulated PBMC from all 47 donors. Ratios are displayed according to the central method for normalization . Light blue and red horizontal bares underline PBMC sample from Caucasian and Chinese donors; in separate panels CD4 (small red horizontal bar) and CD8 T cells (light blue bar) separated by negative bead separation (Miltenyi Biotech, Bergisch Gladbach, Germany) are compared with CD4 and CD8 T cells (orange and dark blue horizontal bars respectively) purified before exposure to rIL-2 – C Top, panel; mRNA expression (expressed as log2 CY5/Cy3) of signal transducers and activators of transcription (STAT)-1, -3 and 5a in non-stimulated PBMC (white bars) or after stimulation with 300 IU/ml of rIL-2 (Blue filled bars). In addition, proportional mRNA levels of three well characterized targets of STAT-5 are shown (CISH, BCL-2 and PIM1); bottom panel: mRNA expression of interferon regulatory factors (IRF) in non-stimulated PBMC (white bars) or after stimulation with 300 IU/ml of rIL-2 (maroon filled bars). Significance is based on a paired two-tailed Student t test between non-stimulated and rIL-2 stimulated samples from all 47 donors (analysis a , table 1).