ADD results section for il2 curves

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Nathan Dwarshuis 2021-07-29 15:07:29 -04:00
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@ -2193,7 +2193,18 @@ Venn diagram from the venn R package.
\subsection{T cells can be grown on DMSs with lower IL2 concentrations} \subsection{T cells can be grown on DMSs with lower IL2 concentrations}
Prior to the main experiments in this aim, we performed a preliminary experiment
to assess the effect of lowering the \gls{il2} concentration on the T cells
grown with either bead or \gls{dms}. One of the hypotheses for the \gls{dms}
system was that the higher cell density would enable more efficient cross-talk
between T cells. Since \gls{il2} is secreted by activated T cells themselves,
T cells in the \gls{dms} system may need less or no \gls{il2} if this hypothesis
were true.
% TODO this plots proportions look dumb % TODO this plots proportions look dumb
% TODO explain what the NLS lines are in b
% TODO plot the differences in lower IL2 concentrations to better show this
\begin{figure*}[ht!] \begin{figure*}[ht!]
\begingroup \begingroup
@ -2217,6 +2228,29 @@ Venn diagram from the venn R package.
\label{fig:il2_mod} \label{fig:il2_mod}
\end{figure*} \end{figure*}
% TODO the nls stuff is a bit iffy
We varied the concentration of \gls{il2} from \SIrange{0}{100}{\IU\per\ml} and
expanded T cells as described in \cref{sec:tcellculture}. T cells grown with
either method expanded robustly as \gls{il2} concentration was increased
(\cref{fig:il2_mod_timecourse}). Surprisingly, neither the bead or the \gls{dms}
group expanded at all with \SI{0}{\IU\per\ml} \gls{il2}. When examining the
endpoint fold change after \SI{14}{\day}, we observe that the difference between
the bead and \gls{dms} appears to be greater at lower \gls{il2} concentrations
(\cref{fig:il2_mod_total}). This is further supported by fitting a non-linear
least squares equation to the data following a hyperbolic curve (which should be
a plausible model given that this curve describes receptor-ligand kinetics,
which we can assume \gls{il2} to follow). Furthermore, the same trend can be
seen when only examining the \ptmem{} cell expansion at day 14
(\cref{fig:il2_mod_mem}). In this case, the \ptmemp{} of the T cells seemed to
be relatively close at higher \gls{il2} concentrations, but separated further at
lower concentrations (\cref{fig:il2_mod_flow})
Taken together, these data do not support the hypothesis that the \gls{dms}
system does not need \gls{il2} at all; however, it appears to have a modest
advantage at lower \gls{il2} concentrations compared to beads. For this reason,
we decided to investigate the lower range of \gls{il2} concentrations starting
at \SI{10}{\IU\per\ml} throughout the remainder of this aim.
% TODO this is not consistent with the next section since the responses are % TODO this is not consistent with the next section since the responses are
% different % different
\subsection{DOE shows optimal conditions for expanded potent T cells} \subsection{DOE shows optimal conditions for expanded potent T cells}