| First Author | Waysbort N | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 12 | Pages | 5822-30 |
| PubMed ID | 24244020 | Mgi Jnum | J:207110 |
| Mgi Id | MGI:5554475 | Doi | 10.4049/jimmunol.1301575 |
| Citation | Waysbort N, et al. (2013) Coupled IL-2-dependent extracellular feedbacks govern two distinct consecutive phases of CD4 T cell activation. J Immunol 191(12):5822-30 |
| abstractText | T cells integrate cell-specific Ag receptor signaling with shared signals mediated by secreted cytokines, which often involve regulatory feedback loops. IL-2 signaling, for example, reduces the synthesis of IL-2 and increases the synthesis of IL-2Ralpha-chain, whereas both genes require TCR signaling for their activation. The ways by which T cells dynamically integrate these private and public signals during activation are not well understood. We combined robotics, multiparameter flow cytometry, and real-time quantitative PCR to analyze T cell activation at high temporal resolution over several days. Two distinct temporal phases of T cell activation were evident. First, Ag-dependent signals activated low IL-2Ralpha and high IL-2 production, independent of IL-2 signaling. Subsequently, secreted IL-2 acted as a shared resource driving high IL-2Ralpha expression, reduced IL-2 synthesis, and cell proliferation. This transition was independent of continued TCR signaling. Our data allowed the determination of the parameters of the IL-2-mediated extracellular positive and negative feedback circuits and demonstrated that the two loops are coupled and become activated at a similar level of IL-2 signaling. We propose that temporal separation of private and shared signals allows T cells to first integrate Ag-specific responses and subsequently share information leading to collective decision making. |
