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

2.50
Hdl Handle:
http://hdl.handle.net/10033/616932
Title:
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
Authors:
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 ( 0000-0002-4300-2474 ) ; Arens, Ramon; Kremer, Melanie; Sutter, Gerd; Messerle, Martin; Förster, Reinhold
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. 2016, 44 (2):233-45 Immunity
Journal:
Immunity
Issue Date:
16-Feb-2016
URI:
http://hdl.handle.net/10033/616932
DOI:
10.1016/j.immuni.2016.01.010
PubMed ID:
26872694
Type:
Article
Language:
en
ISSN:
1097-4180
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorHalle, Stephanen
dc.contributor.authorKeyser, Kirsten Anjaen
dc.contributor.authorStahl, Felix Rolfen
dc.contributor.authorBusche, Andreasen
dc.contributor.authorMarquardt, Anjaen
dc.contributor.authorZheng, Xiangen
dc.contributor.authorGalla, Melanieen
dc.contributor.authorHeissmeyer, Vigoen
dc.contributor.authorHeller, Katrinen
dc.contributor.authorBoelter, Jasminen
dc.contributor.authorWagner, Karenen
dc.contributor.authorBischoff, Yvonneen
dc.contributor.authorMartens, Riekeen
dc.contributor.authorBraun, Asolinaen
dc.contributor.authorWerth, Kathrinen
dc.contributor.authorUvarovskii, Alexeyen
dc.contributor.authorKempf, Haralden
dc.contributor.authorMeyer-Hermann, Michaelen
dc.contributor.authorArens, Ramonen
dc.contributor.authorKremer, Melanieen
dc.contributor.authorSutter, Gerden
dc.contributor.authorMesserle, Martinen
dc.contributor.authorFörster, Reinholden
dc.date.accessioned2016-07-14T10:56:31Z-
dc.date.available2016-07-14T10:56:31Z-
dc.date.issued2016-02-16-
dc.identifier.citationIn Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. 2016, 44 (2):233-45 Immunityen
dc.identifier.issn1097-4180-
dc.identifier.pmid26872694-
dc.identifier.doi10.1016/j.immuni.2016.01.010-
dc.identifier.urihttp://hdl.handle.net/10033/616932-
dc.description.abstractAccording 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.en
dc.language.isoenen
dc.relationnfo:eu-repo/grantAgreement/EC/FP7/322645en
dc.rightsopenAccessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshCalcium Signalingen
dc.subject.meshCell Communicationen
dc.subject.meshCells, Cultureden
dc.subject.meshCytotoxicity, Immunologicen
dc.subject.meshHerpesviridae Infectionsen
dc.subject.meshHumansen
dc.subject.meshImmune Evasionen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshMicroscopy, Fluorescence, Multiphotonen
dc.subject.meshMuromegalovirusen
dc.subject.meshPerforinen
dc.subject.meshT-Lymphocyte Subsetsen
dc.subject.meshT-Lymphocytes, Cytotoxicen
dc.subject.meshVacciniaen
dc.subject.meshVaccinia virusen
dc.titleIn Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalImmunityen

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