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27 results on '"Kretschmer, Lorenz"'

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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6. 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. Early emergence of T central memory precursors programs clonal dominance during chronic viral infection

Author

Grassmann, Simon, Mihatsch, Lorenz, Mir, Jonas, Kazeroonian, Atefeh, Rahimi, Roza, Flommersfeld, Sophie, Schober, Kilian, Hensel, Inge, Leube, Justin, Pachmayr, Ludwig O., Kretschmer, Lorenz, Zhang, Qin, Jolly, Adrien, Chaudhry, M. Zeeshan, Schiemann, Matthias, Cicin-Sain, Luka, Höfer, Thomas, Busch, Dirk H., Flossdorf, Michael, and Buchholz, Veit R.

Published
2020
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13. 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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16. Picking up speed: cell cycle regulation during effector CD8+ T cell differentiation.

Author

Kretschmer, Lorenz, Fuchs, Noémie, Busch, Dirk H., and Buchholz, Veit R.

Subjects
*CELL cycle regulation, *T cell differentiation, *T cells, *IMMUNOLOGIC memory, *FATE mapping (Genetics), *CELL cycle, *T cell receptors
Abstract

Clonal expansion and development of immunological memory are two hallmarks of adaptive immune responses. Resolving the intricate pathways that regulate cell cycle activity and lead to the generation of diverse effector and memory T cell subsets is essential for improving our understanding of protective T cell immunity. A deeper knowledge of cell cycle regulation in T cells also has translational implications for adoptive cell therapies and vaccinations against infectious diseases. Here, we summarize recent evidence for an early diversification of effector and memory CD8+ T cell fates and discuss how this process is coupled to discrete changes in division speed. We further review technical advances in lineage tracing and cell cycle analysis and outline how these techniques have shed new light on the population dynamics of CD8+ T cell responses, thereby refining our current understanding of the developmental organization of the memory T cell pool. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Single‐cell fate mapping reveals widespread clonal ignorance of low‐affinity T cells exposed to systemic infection.

Author

Leube, Justin, Mühlbauer, Anton, Andrä, Immanuel, Biggel, Madleen, Busch, Dirk H., Kretschmer, Lorenz, and Buchholz, Veit R.

Subjects
T cells, IMMUNOLOGICAL tolerance, T cell receptors
Abstract

T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen‐specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self‐antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen‐specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single‐cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high‐affinity antigen‐specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low‐affinity antigen‐specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high‐affinity ligand. These data establish the widespread clonal ignorance of low‐affinity T cells as a major factor shaping the composition of antigen‐specific CD8+ T cell responses to systemic infection. [ABSTRACT FROM AUTHOR]

Published
2023
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18. 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

19. 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

20. 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

26. Disparate Individual Fates Compose Robust CD8 + T Cell Immunity

Author

Buchholz, Veit R., primary, Flossdorf, Michael, additional, Hensel, Inge, additional, Kretschmer, Lorenz, additional, Weissbrich, Bianca, additional, Gräf, Patricia, additional, Verschoor, Admar, additional, Schiemann, Matthias, additional, Höfer, Thomas, additional, and Busch, Dirk H., additional

Published
2013
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27. 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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