Cytokine niches in evolution of the immune response in T cell cultures

by Mr. Barak Azoulai

Dept. Of Physics, Ben-Gurion University

at Biological and soft-matter physics

Thu, 29 Oct 2020, 12:00
ZOOM only - *Meeting ID CHANGED*: 841 9016 0947

Abstract

A healthy immune system is a system that can on one hand identify, contain, and eliminate
huge diversity of pathogenic threats and on the other hand avoid erroneous recognition
of self or not threatening antigens, while doing it with the minimal damage to the host
tissue. Maintaining this balance requires tight coordination between the different immune
cells. This coordination occurs mostly through the exchange of small signalling molecules,
called cytokines, that bind to specific receptors on the target cells and transmit information
regarding the state of the producer. As a result of signalling by these cytokines, the cells
will typically undergo phenotypic changes (e.g. proliferation, death, differentiation and etc).

Essential aspects of this communication that remain poorly-understood are its charac
teristic length scale and the evolution of the latter as the environment receptor numbers
changes in response to the cytokine signalling. In this study we focused on the example of
Interleukin-2 (IL-2) cytokine and the α unit of its receptor (IL-2Rα), we aim at the quan
titative understanding of the co-evolution of a cytokine and its receptor fields around an
activated T cell that secretes the cytokine.

We describe the spatio-temporal dynamics of the system within a mathematical frame
work that incorporates a sink-diffusion equation for the cytokine and a simple rate equation
for the receptor evolution taking into account their natural degradation and the positive
feedback mechanism between IL-2 signalling and IL-2Rα expression. Furthermore, we de
velop the experimental approach to monitor the IL-2/IL-2Rα spatio-temporal dynamics in
T cell cultures, and model it with computer simulation code we wrote.

We observe in experiments that in the course of T cell culture evolution the IL-2 and
IL-2Rα fields tend to co-localize around the secreting cell. This co-localization occurs due
to the positive feedback between the IL-2 signalling and IL-2Rα expression. The measured
data are well described by both our analytical model and computer simulations.

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Meeting ID: 841 9016 0947

Created on 18-10-2020 by Granek, Rony (rgranek)
Updaded on 28-10-2020 by Granek, Rony (rgranek)