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The role of receptor signaling in immunological memory. (A) Long-term immunological memory in CD4 T cells is dependent on cytokine and TNFSF networks involving interleukin 7 (IL-7) and OX40 that maintain the rapid recall response in CD4 memory T cells. Stroma-derived IL-7 upregulates expression of OX40, the receptor for OX40L, which is produced by antigen-presenting cells. (B) Multiple signaling pathways are predicted to reinforce epigenetic priming in memory T cells. T cell receptor (TCR) signaling activates both NFAT and AP-1 that cooperate to transiently induce DNase I hypersensitive sites (DHSs) at enhancers and trigger the establishment of primed DHSs. Once priming is established, cytokine and TNFSF signaling pathways can subsequently induce AP-1 and/or STAT family transcription factors (but not NFAT) which are predicted to reinforce the priming that was initially introduced via TCR signaling.