Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28355549
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biophys+J
2017 ; 112
(6
): 1221-1235
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
A Sigmoid Functional Response Emerges When Cytotoxic T Lymphocytes Start Killing
Fresh Target Cells
#MMPMID28355549
Gadhamsetty S
; Marée AFM
; Beltman JB
; de Boer RJ
Biophys J
2017[Mar]; 112
(6
): 1221-1235
PMID28355549
show ga
Cytotoxic T lymphocyte (CTL)-mediated killing involves the formation of a synapse
with a target cell, followed by delivery of perforin and granzymes. Previously,
we derived a general functional response for CTL killing while considering that
CTLs form stable synapses (i.e., single-stage) and that the number of conjugates
remains at steady state. However, the killing of target cells sometimes requires
multiple engagements (i.e., multistage). To study how multistage killing and a
lack of steady state influence the functional response, we here analyze a set of
differential equations as well as simulations employing the cellular Potts model,
in both cases describing CTLs that kill target cells. We find that at steady
state the total killing rate (i.e., the number of target cells killed by all
CTLs) is well described by the previously derived double saturation function.
Compared to single-stage killing, the total killing rate during multistage
killing saturates at higher CTL and target cell densities. Importantly, when the
killing is measured before the steady state is approached, a qualitatively
different functional response emerges for two reasons: First, the killing signal
of each CTL gets diluted over several targets and because this dilution effect is
strongest at high target cell densities; this can result in a peak in the
dependence of the total killing rate on the target cell density. Second, the
total killing rate exhibits a sigmoid dependence on the CTL density when killing
is a multistage process, because it takes typically more than one CTL to kill a
target. In conclusion, a sigmoid dependence of the killing rate on the CTLs
during initial phases of killing may be indicative of a multistage killing
process. Observation of a sigmoid functional response may thus arise from a
dilution effect and is not necessarily due to cooperative behavior of the CTLs.