Author(s): Waysbort N, Russ D, Chain BM, Friedman N
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-2Rα-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-2Rα and high IL-2 production, independent of IL-2 signaling. Subsequently, secreted IL-2 acted as a shared resource driving high IL-2Rα 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.
Referred From: http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.1301575
Author(s): Chase EP, Armstrong AW
Author(s): Riechelmann H, Essig A, Deutschle T
Author(s): Tang VH, Chang BJ, Srinivasan A, Leslie T. Mathaba, Gerald B. Harnett, et al.
Author(s): Bogdali AM, Antoszczyk G, Dyga W, Obtulowicz
Author(s): Eyerich K and Novak N