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Halle, S.* ; Keyser, K.A.* ; Stahl, F.R.* ; 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.* ; Forster, R.*

In vivo killing capacity of cytotoxic T cells is limited and involves dynamic interactions and T cell cooperativity.

Immunity 44, 233-245 (2016)
Verlagsversion DOI
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Immune-system; Lymph-node; Cytomegalovirus; Memory; Virus; Synapses; Differentiation; Lymphocytes; Secretion; Migration
ISSN (print) / ISBN 1074-7613
e-ISSN 1097-4180
Zeitschrift Immunity
Quellenangaben Band: 44, Heft: 2, Seiten: 233-245 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed