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Immunity. 2016 Feb 16;44(2):233-45. doi: 10.1016/j.immuni.2016.01.010. Epub 2016 Feb 9.

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

Author information

1
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: halle.stephan@mh-hannover.de.
2
Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.
3
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
4
Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
5
Institute for Immunology, Ludwig-Maximilians-Universität München, 80336 München, Germany; Institute of Molecular Immunology, Helmholtz Zentrum München, 81377 München, Germany.
6
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
7
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Institute for Biochemistry, Biotechnology, and Bioinformatics, Technische Universität Braunschweig, 38124 Braunschweig, Germany.
8
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
9
Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universität München, 80539 München, Germany.
10
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: foerster.reinhold@mh-hannover.de.

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.

PMID:
26872694
PMCID:
PMC4846978
DOI:
10.1016/j.immuni.2016.01.010
[Indexed for MEDLINE]
Free PMC Article

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