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In vivo killing capacity of cytotoxic T cells is limited and involves dynamic interactions and T cell cooperativity.
Immunity 44, 233-245 (2016)
Publ. Version/Full Text
DOI
PMC
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Immune-system; Lymph-node; Cytomegalovirus; Memory; Virus; Synapses; Differentiation; Lymphocytes; Secretion; Migration
ISSN (print) / ISBN
1074-7613
e-ISSN
1097-4180
Journal
Immunity
Quellenangaben
Volume: 44,
Issue: 2,
Pages: 233-245
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Abteilung für Molekulare Immunregulation (AMIR)