In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity

Stephan Halle, Kirsten Anja Keyser, Felix Rolf Stahl, Andreas Busche, Anja Marquardt, Xiang Zheng, Melanie Galla, Vigo Heissmeyer, Katrin Heller, Jasmin Boelter, Karen Wagner, Yvonne Bischoff, Rieke Martens, Asolina Braun, Kathrin Werth, Alexey Uvarovskii, Harald Kempf, Michael Meyer-Hermann, Ramon Arens, Melanie KremerGerd Sutter, Martin Messerle, Reinhold Förster

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89 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)233-245
Number of pages13
JournalImmunity
Volume44
Issue number2
DOIs
Publication statusPublished - 16 Feb 2016
Externally publishedYes

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