In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
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Authors
Halle, StephanKeyser, Kirsten Anja
Stahl, Felix Rolf
Busche, Andreas
Marquardt, Anja
Zheng, Xiang
Galla, Melanie
Heissmeyer, Vigo
Heller, Katrin
Boelter, Jasmin
Wagner, Karen
Bischoff, Yvonne
Martens, Rieke
Braun, Asolina
Werth, Kathrin
Uvarovskii, Alexey
Kempf, Harald
Meyer-Hermann, Michael
Arens, Ramon
Kremer, Melanie
Sutter, Gerd
Messerle, Martin
Förster, Reinhold
Issue Date
2016-02-16
Metadata
Show full item recordAbstract
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.Citation
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. 2016, 44 (2):233-45 ImmunityAffiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
ImmunityPubMed ID
26872694Type
ArticleLanguage
enISSN
1097-4180ae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2016.01.010
Scopus Count
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- Creative Commons