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1. Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Author

Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.

Published
2024
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2. Author Correction: Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Author

Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.

Published
2024
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5. MYB orchestrates T cell exhaustion and response to checkpoint inhibition

Author

Tsui, Carlson, Kretschmer, Lorenz, Rapelius, Svenja, Gabriel, Sarah S., Chisanga, David, Knöpper, Konrad, Utzschneider, Daniel T., Nüssing, Simone, Liao, Yang, Mason, Teisha, Torres, Santiago Valle, Wilcox, Stephen A., Kanev, Krystian, Jarosch, Sebastian, Leube, Justin, Nutt, Stephen L., Zehn, Dietmar, Parish, Ian A., Kastenmüller, Wolfgang, Shi, Wei, Buchholz, Veit R., and Kallies, Axel

Published
2022
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8. CagA-specific Gastric CD8+ Tissue-Resident T Cells Control Helicobacter pylori During the Early Infection Phase

Author

Koch, Maximilian R., primary, Gong, Ruolan, additional, Friedrich, Verena, additional, Engelsberger, Veronika, additional, Kretschmer, Lorenz, additional, Wanisch, Andreas, additional, Jarosch, Sebastian, additional, Ralser, Anna, additional, Lugen, Bob, additional, Quante, Michael, additional, Vieth, Michael, additional, Vasapolli, Riccardo, additional, Schulz, Christian, additional, Buchholz, Veit R., additional, Busch, Dirk H., additional, Mejías-Luque, Raquel, additional, and Gerhard, Markus, additional

Published
2022
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9. Antigen-Abhängigkeit der Zellzyklusgeschwindigkeit während der primären Aktivierung formt das CD8+ T-Zell-Gedächtnis

Author

Kretschmer, Lorenz Christoph Benjamin, Busch, Dirk (Prof. Dr.), Poeck, Hendrik (Priv.-Doz. Dr.), and Schmidt-Supprian, Marc (Prof. Dr.)

Subjects
Medizin und Gesundheit, ddc:610
Abstract

In this work, the development of immune responses derived from single naive CD8+ T cells was studied. It was found that the precursors of central memory T cells displayed slower cell cycle speeds than those of short-lived effector T cells, already during the early stages of the clonal expansion phase. Upon premature depletion of antigen-presenting dendritic cells, the cell cycle of these central memory precursors was further delayed and the generation of secondary immune responses was impaired. In dieser Arbeit wurde die Entwicklung von Immunantworten ausgehend von einzelnen naiven CD8+ T-Zellen untersucht. Dabei zeigte sich, dass die Vorläufer zentraler Gedächtnis-T-Zellen schon während der frühen Expansionsphase einen langsameren Zellzyklus aufweisen, als diejenigen kurzlebiger Effektor-T-Zellen. Nach vorzeitiger Depletion Antigen-präsentierender Dendritischer Zellen wurde der Zellzyklus dieser zentralen Gedächtnisvorläufer weiter verlangsamt und die Ausbildung sekundärer Immunantworten war gestört.

Published
2021

10. Antigen-dependence of cell cycle speed during priming shapes CD8+ T cell memory

Author

Poeck, Hendrik (Priv.-Doz. Dr.), Busch, Dirk (Prof. Dr.), Schmidt-Supprian, Marc (Prof. Dr.), Kretschmer, Lorenz Christoph Benjamin, Poeck, Hendrik (Priv.-Doz. Dr.), Busch, Dirk (Prof. Dr.), Schmidt-Supprian, Marc (Prof. Dr.), and Kretschmer, Lorenz Christoph Benjamin

Abstract

In this work, the development of immune responses derived from single naive CD8+ T cells was studied. It was found that the precursors of central memory T cells displayed slower cell cycle speeds than those of short-lived effector T cells, already during the early stages of the clonal expansion phase. Upon premature depletion of antigen-presenting dendritic cells, the cell cycle of these central memory precursors was further delayed and the generation of secondary immune responses was impaired., In dieser Arbeit wurde die Entwicklung von Immunantworten ausgehend von einzelnen naiven CD8+ T-Zellen untersucht. Dabei zeigte sich, dass die Vorläufer zentraler Gedächtnis-T-Zellen schon während der frühen Expansionsphase einen langsameren Zellzyklus aufweisen, als diejenigen kurzlebiger Effektor-T-Zellen. Nach vorzeitiger Depletion Antigen-präsentierender Dendritischer Zellen wurde der Zellzyklus dieser zentralen Gedächtnisvorläufer weiter verlangsamt und die Ausbildung sekundärer Immunantworten war gestört.

Published
2021

11. Antigen-dependence of cell cycle speed during priming shapes CD8+ T cell memory

Author

Busch, Dirk (Prof. Dr.), Busch, Dirk (Prof. Dr.);Poeck, Hendrik (Priv.-Doz. Dr.);Schmidt-Supprian, Marc (Prof. Dr.), Kretschmer, Lorenz Christoph Benjamin, Busch, Dirk (Prof. Dr.), Busch, Dirk (Prof. Dr.);Poeck, Hendrik (Priv.-Doz. Dr.);Schmidt-Supprian, Marc (Prof. Dr.), and Kretschmer, Lorenz Christoph Benjamin

Abstract

In this work, the development of immune responses derived from single naive CD8+ T cells was studied. It was found that the precursors of central memory T cells displayed slower cell cycle speeds than those of short-lived effector T cells, already during the early stages of the clonal expansion phase. Upon premature depletion of antigen-presenting dendritic cells, the cell cycle of these central memory precursors was further delayed and the generation of secondary immune responses was impaired., In dieser Arbeit wurde die Entwicklung von Immunantworten ausgehend von einzelnen naiven CD8+ T-Zellen untersucht. Dabei zeigte sich, dass die Vorläufer zentraler Gedächtnis-T-Zellen schon während der frühen Expansionsphase einen langsameren Zellzyklus aufweisen, als diejenigen kurzlebiger Effektor-T-Zellen. Nach vorzeitiger Depletion Antigen-präsentierender Dendritischer Zellen wurde der Zellzyklus dieser zentralen Gedächtnisvorläufer weiter verlangsamt und die Ausbildung sekundärer Immunantworten war gestört.

Published
2021

16. TCR Signal Quality Modulates Fate Decisions of Single CD4+T Cells in a Probabilistic Manner

Author

Cho, Yi-Li, Flossdorf, Michael, Kretschmer, Lorenz, Höfer, Thomas, Busch, Dirk H., and Buchholz, Veit R.

Abstract

To what extent the lineage decisions of activated CD4+T cells are determined by the quality of T cell receptor (TCR) ligation is incompletely understood. Here, we show that individual T cells expressing identical TCRs take highly variable fate decisions despite binding the same ligand. We identify a mathematical model that correctly captures this probabilistic behavior and allows one to formalize changes in TCR signal quality—due to cognate versus altered peptide ligation—as changes of lineage-specific proliferation and differentiation rates. We show that recall responses also adhere to this probabilistic framework requiring recruitment of multiple memory clones to provide reliable differentiation patterns. By extending our framework to simulate hypothetical TCRs of distinct binding strength, we reconstruct primary and secondary response patterns emerging from a polyclonal TCR repertoire in silico. Collectively, these data suggest that individual T cells harboring distinct TCRs generate overlapping primary differentiation patterns that segregate only upon repetitive immunization.

Published
2017
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