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  • Title: Hyporesponsiveness of CD4 T cells induced in oral tolerance is maintained by selective impairment in the TCR-induced calcium/NFAT signaling pathway resulting from caspase activation.
    Author: Hachimura S, Kaji T, Asai K, Ise W, Nakayama T, Kaminogawa S.
    Journal: Ann N Y Acad Sci; 2004 Dec; 1029():344-5. PubMed ID: 15681776.
    Abstract:
    We examined intracellular signaling of hyporesponsive CD4 T cells induced by continuous feeding with high-dose antigen in a TCR transgenic mouse system. The results demonstrated a selective impairment in their TCR-induced calcium/NFAT-signaling pathway. Proteomic analysis revealed caspase activation in these cells, which resulted in cleavage of GADS. Further analysis of the TCR-signaling complex showed that GADS-LAT-SLP-76-associated PLC-gamma1 was decreased in both phosphorylation and association. Thus, as a consequence of caspase activation, orally tolerant CD4 T cells could not form normal TCR signaling complexes associated with GADS and showed downregulated PLC-gamma1 activation, which resulted in impairment of TCR-induced calcium signaling.
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