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 Kremer & 3 others Gerd Sutter, Martin Messerle, Reinhold Förster

Research output: Contribution to journalArticleResearchpeer-review

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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.

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

Cite this

Halle, S., Keyser, K. A., Stahl, F. R., Busche, A., Marquardt, A., Zheng, X., ... Förster, R. (2016). In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. Immunity, 44(2), 233-245. https://doi.org/10.1016/j.immuni.2016.01.010
Halle, Stephan ; Keyser, 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. / In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. In: Immunity. 2016 ; Vol. 44, No. 2. pp. 233-245.
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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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Halle, S, Keyser, KA, Stahl, FR, Busche, A, Marquardt, A, Zheng, X, Galla, M, Heissmeyer, V, Heller, K, Boelter, J, Wagner, K, Bischoff, Y, Martens, R, Braun, A, Werth, K, Uvarovskii, A, Kempf, H, Meyer-Hermann, M, Arens, R, Kremer, M, Sutter, G, Messerle, M & Förster, R 2016, 'In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity', Immunity, vol. 44, no. 2, pp. 233-245. https://doi.org/10.1016/j.immuni.2016.01.010

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; 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.

In: Immunity, Vol. 44, No. 2, 16.02.2016, p. 233-245.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Halle, Stephan

AU - Keyser, Kirsten Anja

AU - Stahl, Felix Rolf

AU - Busche, Andreas

AU - Marquardt, Anja

AU - Zheng, Xiang

AU - Galla, Melanie

AU - Heissmeyer, Vigo

AU - Heller, Katrin

AU - Boelter, Jasmin

AU - Wagner, Karen

AU - Bischoff, Yvonne

AU - Martens, Rieke

AU - Braun, Asolina

AU - Werth, Kathrin

AU - Uvarovskii, Alexey

AU - Kempf, Harald

AU - Meyer-Hermann, Michael

AU - Arens, Ramon

AU - Kremer, Melanie

AU - Sutter, Gerd

AU - Messerle, Martin

AU - Förster, Reinhold

PY - 2016/2/16

Y1 - 2016/2/16

N2 - 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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DO - 10.1016/j.immuni.2016.01.010

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