Zeitschrift für klinische und zelluläre Immunologie
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New Paradigm of T cell Signaling: Learning from Malignancies

Makoto Yamagishi and Toshiki Watanabe

T cells are key mediators of cell-mediated immunity. Their functions and proliferation result from T cell-specific receptor signaling (TCR/CD28) that activates the NF-κB, NFAT, Ras-MAPK, and PI3K-Akt pathways. Their development and activation also involve a complex array of signaling pathways that regulate gene expression networks, including signaling of mTOR, Notch, Wnt, Hedgehog, TGF-β, and toll-like receptors. Furthermore, recent discoveries have provided two molecular hallmarks of potential generality: miRNA patterns and polycomb-mediated epigenetic reprogramming, which can strongly coordinate the balance between molecular networks in lymphocytes. Their deregulation apparently causes T cell disorders, such as T cell acute lymphoblastic leukemia (T-ALL), and human T cell leukemia virus (HTLV-1)-induced adult T cell leukemia (ATL). This review continues with a description of our understanding of crosstalk among the signaling pathways, which contribute to the highly orchestrated development of T cell fate specification under both normal physiological and pathological conditions.