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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2016 Feb 14

PMID 26872694

Citations 120

Authors

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

Gerd Sutter

Martin Messerle

Reinhold Forster

Affiliations

Soon will be listed here.

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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