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lüll Negative regulators in homeostasis of naive peripheral T cells Modiano JF; Johnson LD; Bellgrau DImmunol Res 2008[]; 41 (2): 137-53It is now apparent that naive peripheral T cells are a dynamic population where active processes prevent inappropriate activation while supporting survival. The process of thymic education makes naive peripheral T cells dependent on interactions with self-MHC for survival. However, as these signals can potentially result in inappropriate activation, various non-redundant, intrinsic negative regulatory molecules including Tob, Nfatc2, and Smad3 actively enforce T cell quiescence. Interactions among these pathways are only now coming to light and may include positive or negative crosstalk. In the case of positive crosstalk, self-MHC initiated signals and intrinsic negative regulatory factors may cooperate to dampen T cell activation and sustain peripheral tolerance in a binary fashion (on-off). In the case of negative crosstalk, self-MHC signals may promote survival through partial activation while intrinsic negative regulatory factors act as rheostats to restrain cell cycle entry and prevent T cells from crossing a threshold that would break tolerance.|Animals[MESH]|Cell Proliferation[MESH]|GTP-Binding Proteins/metabolism[MESH]|Homeostasis[MESH]|Humans[MESH]|Lymphocyte Activation[MESH]|Major Histocompatibility Complex/*immunology[MESH]|NFATC Transcription Factors/metabolism[MESH]|Protein Kinases/metabolism[MESH]|Signal Transduction[MESH]|Smad3 Protein/metabolism[MESH]|T-Lymphocyte Subsets/*immunology/metabolism[MESH]|Tumor Suppressor Proteins/metabolism[MESH] |