The effects of interleukin-2 on immune response regulation.
The immune system has many adaptive and dynamic components that are regulated to ensure appropriate, precise and rapid response to a foreign pathogen. A delayed or inadequate immune response can lead to prolonged disease, while an excessive or under-regulated response can lead to autoimmunity. The cytokine, interleukin-2 (IL-2) and its receptor IL-2R play an important role in maintaining this balance.The IL-2 receptor transduces pSTAT5 signal through both the intermediate and high affinity receptors, which differ from each other by the presence of CD25 chain in IL-2 receptor. We present experimental data on the kinetics of pSTAT5 signalling through both of the receptors and develop a model that captures this kinetics. We then use this model to parameterize key aspects of two additional models in which we propose and study two different mechanisms by which IL-2 receptor can transduce distinct signals leading to either an activated or a non-activated cell state. We speculate that this initial state differentiation, perhaps enhanced by downstream feedbacks, may eventually lead to differential cell fates.Our result shows that non-linear dynamical models can suggest resolution of a puzzling array of seemingly contradictory experimental results on IL-2 effect on proliferation and differentiation of T-cells.
Department of Mathematical Sciences, Montana State University, Bozeman, MT, MT.
Ryan S
RS
Waters
Neuroimmunological Diseases Unit, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, VA.
Justin S A
JSA
Perry
Neuroimmunological Diseases Unit, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD.
SunPil
S
Han
Neuroimmunological Diseases Unit, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD.
Bibiana
B
Bielekova
Department of Mathematical Sciences, Montana State University, Bozeman, MT, MT.
Tomas
T
Gedeon
D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000077561:Daclizumab; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism*; D008962:Models, Theoretical; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; D000077561:Daclizumab