| First Author | Sojka DK | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 11 | Pages | 7274-80 |
| PubMed ID | 16301632 | Mgi Jnum | J:122145 |
| Mgi Id | MGI:3713408 | Doi | 10.4049/jimmunol.175.11.7274 |
| Citation | Sojka DK, et al. (2005) Early kinetic window of target T cell susceptibility to CD25+ regulatory T cell activity. J Immunol 175(11):7274-80 |
| abstractText | Peripheral tolerance is maintained in part by thymically derived CD25+CD4+ T cells (regulatory T cells (Tregs)). Their mechanism of action has not been well characterized. Therefore, to get a better understanding of Treg action, we investigated the kinetics of murine Treg activity in vitro. Tregs were suppressive within a surprisingly narrow kinetic window: necessary and sufficient only in the first 6-10 h of culture. Visualization of this time frame, using a sensitive single-cell assay for IL-2, revealed the early elaboration of target cell IL-2 producers in the first 6 h despite the presence of CD25+CD4+ Tregs. However, after 6 h, a rapid rise in the number of IL-2 producers in the absence of Tregs was dramatically abrogated by the presence of Tregs. Importantly, the timing of suppression was dictated by the kinetics of target T cell activation suggesting that early target T cell signals may alter susceptibility to suppression. Modulating target T cell activation signals with provision of CD28, IL-2, or high Ag dose all abrogated suppression of proliferation late in culture. However, only CD28 signals enabled target T cells to resist the early Treg-induced down-regulation of IL-2. Therefore the quality of early target T cell activation signals, in particular engagement of CD28, represents an important control point in the balance between vulnerability and resistance to Treg suppression. |
