Negative regulators in homeostasis of naïve peripheral T cells.
It is now apparent that naïve peripheral T cells are a dynamic population where active processes prevent inappropriate activation while supporting survival. The process of thymic education makes naïve 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.
Modiano
Jaime F
JF
Integrated Department of Immunology, University of Colorado-Denver, Denver, CO, USA. modiano@umn.edu
Johnson
Lisa D S
LD
Bellgrau
Donald
D
D000818:Animals; D049109:Cell Proliferation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D050778:NFATC Transcription Factors; D051900:Smad3 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D019204:GTP-Binding Proteins