Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness.
Linda E. Kippner,Melissa L. Kemp +1 more
Reads0
Chats0
TLDR
In vitro results demonstrate that single cell response profiles vary with pulsatile IL-2 input at pre-equilibrium levels, which confirmed the model predictions that Jurkat cells have a preferred range of extracellularIL-2 fluctuations, in which downstream response is rapidly initiated.Abstract:
Cell response to extracellular ligand is affected not only by ligand availability, but also by pre-existing cell-to-cell variability that enables a range of responses within a cell population We developed a computational model that incorporates cell heterogeneity in order to investigate Jurkat T cell response to time dependent extracellular IL-2 stimulation Our model predicted preferred timing of IL-2 oscillatory input for maximizing downstream intracellular STAT5 nuclear translocation The modeled cytokine exposure was replicated experimentally through the use of a microfluidic platform that enabled the parallelized capture of dynamic single cell response to precisely delivered pulses of IL-2 stimulus The in vitro results demonstrate that single cell response profiles vary with pulsatile IL-2 input at pre-equilibrium levels These observations confirmed our model predictions that Jurkat cells have a preferred range of extracellular IL-2 fluctuations, in which downstream response is rapidly initiated Further investigation into this filtering behavior could increase our understanding of how pre-existing cellular states within immune cell populations enable a systems response within a preferred range of ligand fluctuations, and whether the observed cytokine range corresponds to in vivo conditionsread more
References
More filters
Journal ArticleDOI
Selective in vitro growth of T lymphocytes from normal human bone marrows
TL;DR: The T cells exhibited a strict growth dependence upon Phytohemagglutinin-stimulated normal human lymphocytes and were consistently negative for Epstein-Barr viral information.
Journal ArticleDOI
Interleukin-2: inception, impact, and implications.
TL;DR: Because T cell clonal proliferation after antigen challenge is obligatory for immune responsiveness and immune memory, the IL-2-T cell system has opened the way to a molecular understanding of phenomena that are fundamental to biology, immunology, and medicine.
Journal ArticleDOI
Interleukin 15: biology and relevance to human disease
TL;DR: The cloning of interleukin (IL)-15 and IL-2 have similar biologic properties in vitro, consistent with their shared receptor (R) signaling components (IL-2/15Rβγc).
Journal ArticleDOI
Cloning of the gamma chain of the human IL-2 receptor
Toshikazu Takeshita,Hironobu Asao,Kiyoshi Ohtani,Naoto Ishii,Satoru Kumaki,Nobuyuki Tanaka,Hiroshi Munakata,Masataka Nakamura,Kazuo Sugamura +8 more
TL;DR: A third subunit, the gamma chain, of the human interleukin-2 receptor (IL-2R) was identified, and a complementary DNA clone encoding this member of the cytokine receptor family was isolated.
Journal ArticleDOI
The IL -2 IL-2 receptor system: A current overview
TL;DR: The IL-2 system has been extensively studied in the context of the clonal proliferation of T cells and has become a paradigm of how interleukins and other soluble mediators, collectively termed cyto- kines, function in the development and regulation of the immune system.