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In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
Halle, Stephan Keyser, Kirsten Anja Stahl, Felix Rolf Busche, Andreas Marquardt, Anja Zheng, Xiang Galla, Melanie Heissmeyer, Vigo Heller, Katrin Boelter, Jasmin
Halle, Stephan
Keyser, Kirsten Anja
Stahl, Felix Rolf
Busche, Andreas
Marquardt, Anja
Zheng, Xiang
Galla, Melanie
Heissmeyer, Vigo
Heller, Katrin
Boelter, Jasmin
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2016-02-16
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Abstract
According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL)-mediated killing of virus-infected cells in vivo remains elusive. We used two-photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2-16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8(+) T cell immunity.
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In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. 2016, 44 (2):233-45 Immunity
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en
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1097-4180
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openAccess