Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 137-153 |
Number of pages | 17 |
Journal | Immunologic Research |
Volume | 41 |
Issue number | 2 |
DOIs | |
State | Published - Jun 1 2008 |
Keywords
- Cell cycle
- Desensitization
- MHC
- Negative regulation
- Sensitization
- T cells
- Tolerance