Interleukin 2 (IL-2) and Janus kinase (JAK) regulate T cell biology by the co-ordinated phosphorylation of transcription factors, regulators of chromatin, mRNA translation, GTPases, vesicle trafficking and the actin and microtubule cytoskeleton. A key role for IL-2 is to control the transcriptional programs in T cells but IL-2/JAK signaling also regulates mRNA translation and protein synthesis to control T cell growth. To explore IL-2 and JAK control T cell function we have used high resolution mass spectrometry to quantify how IL-2 and Jak kinase inhibitors configure the proteomes of CD4 TH1 cells and CD8+ cytotoxic T cells. We show that IL-2/JAK signaling regulates the expression of critical transcription factors, nutrient transporters, ribosomal proteins and metabolic enzymes to sustain the integrity of core metabolic processes essential for cellular fitness. One novel insight is that IL-2/JAK signaling regulates expression of the transcription factor NFIL3 (E4BP4) via control of the HIF1a transcription factor complex. These data reveal a fundamental IL-2 controlled signaling mechanism linking oxygen sensing to transcriptional control of T cell differentiation. These data inform how IL-2 controls effector T cell responses to hypoxia and provide a molecular understanding of how inhibitors of JAK kinases limit T cell function.