Publication

TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall

Cebula, M., Riehn, M., Hillebrand, U., Kratzer, R. F., Kreppel, F., Koutsoumpli, G., Daemen, T., Hauser, H. & Wirth, D., 4-Oct-2017, In : Molecular Therapy. 25, 10, p. 2289-2298 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Cebula, M., Riehn, M., Hillebrand, U., Kratzer, R. F., Kreppel, F., Koutsoumpli, G., ... Wirth, D. (2017). TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall. Molecular Therapy, 25(10), 2289-2298. https://doi.org/10.1016/j.ymthe.2017.06.018

Author

Cebula, Marcin ; Riehn, Mathias ; Hillebrand, Upneet ; Kratzer, Ramona F ; Kreppel, Florian ; Koutsoumpli, Georgia ; Daemen, Toos ; Hauser, Hansjörg ; Wirth, Dagmar. / TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall. In: Molecular Therapy. 2017 ; Vol. 25, No. 10. pp. 2289-2298.

Harvard

Cebula, M, Riehn, M, Hillebrand, U, Kratzer, RF, Kreppel, F, Koutsoumpli, G, Daemen, T, Hauser, H & Wirth, D 2017, 'TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall', Molecular Therapy, vol. 25, no. 10, pp. 2289-2298. https://doi.org/10.1016/j.ymthe.2017.06.018

Standard

TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall. / Cebula, Marcin; Riehn, Mathias; Hillebrand, Upneet; Kratzer, Ramona F; Kreppel, Florian; Koutsoumpli, Georgia; Daemen, Toos; Hauser, Hansjörg; Wirth, Dagmar.

In: Molecular Therapy, Vol. 25, No. 10, 04.10.2017, p. 2289-2298.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Cebula M, Riehn M, Hillebrand U, Kratzer RF, Kreppel F, Koutsoumpli G et al. TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall. Molecular Therapy. 2017 Oct 4;25(10):2289-2298. https://doi.org/10.1016/j.ymthe.2017.06.018


BibTeX

@article{43d56879e84542929e2c74e2a73f976e,
title = "TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall",
abstract = "Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients. Vaccination induced endogenous CD8 T cells could eliminate low antigen loads in liver but were functionally impaired if confronted with elevated antigen loads. Strikingly, only by conditioning the liver environment with TLR9 ligand prior and early after peripheral vaccination, successful immunization against high intrahepatic antigen density with its elimination was achieved. Moreover, TLR9 immunomodulation was also indispensable for functional memory recall after high frequency antigen challenge. Together, the results indicate that TLR9-mediated conditioning of liver environment during therapeutic vaccination or antigen reoccurrence is crucial for an efficacious intrahepatic T cell response.",
keywords = "CD8(+) T-CELLS, C VIRUS-INFECTION, IMMUNE-RESPONSES, HEPATITIS-B, THERAPEUTIC VACCINATION, ADENOVIRUS VECTORS, CERVICAL-CANCER, CD8+T CELLS, ANTIGEN, HEPATOCYTES",
author = "Marcin Cebula and Mathias Riehn and Upneet Hillebrand and Kratzer, {Ramona F} and Florian Kreppel and Georgia Koutsoumpli and Toos Daemen and Hansj{\"o}rg Hauser and Dagmar Wirth",
note = "Copyright {\circledC} 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = "10",
day = "4",
doi = "10.1016/j.ymthe.2017.06.018",
language = "English",
volume = "25",
pages = "2289--2298",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "CELL PRESS",
number = "10",

}

RIS

TY - JOUR

T1 - TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall

AU - Cebula, Marcin

AU - Riehn, Mathias

AU - Hillebrand, Upneet

AU - Kratzer, Ramona F

AU - Kreppel, Florian

AU - Koutsoumpli, Georgia

AU - Daemen, Toos

AU - Hauser, Hansjörg

AU - Wirth, Dagmar

N1 - Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

PY - 2017/10/4

Y1 - 2017/10/4

N2 - Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients. Vaccination induced endogenous CD8 T cells could eliminate low antigen loads in liver but were functionally impaired if confronted with elevated antigen loads. Strikingly, only by conditioning the liver environment with TLR9 ligand prior and early after peripheral vaccination, successful immunization against high intrahepatic antigen density with its elimination was achieved. Moreover, TLR9 immunomodulation was also indispensable for functional memory recall after high frequency antigen challenge. Together, the results indicate that TLR9-mediated conditioning of liver environment during therapeutic vaccination or antigen reoccurrence is crucial for an efficacious intrahepatic T cell response.

AB - Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients. Vaccination induced endogenous CD8 T cells could eliminate low antigen loads in liver but were functionally impaired if confronted with elevated antigen loads. Strikingly, only by conditioning the liver environment with TLR9 ligand prior and early after peripheral vaccination, successful immunization against high intrahepatic antigen density with its elimination was achieved. Moreover, TLR9 immunomodulation was also indispensable for functional memory recall after high frequency antigen challenge. Together, the results indicate that TLR9-mediated conditioning of liver environment during therapeutic vaccination or antigen reoccurrence is crucial for an efficacious intrahepatic T cell response.

KW - CD8(+) T-CELLS

KW - C VIRUS-INFECTION

KW - IMMUNE-RESPONSES

KW - HEPATITIS-B

KW - THERAPEUTIC VACCINATION

KW - ADENOVIRUS VECTORS

KW - CERVICAL-CANCER

KW - CD8+T CELLS

KW - ANTIGEN

KW - HEPATOCYTES

U2 - 10.1016/j.ymthe.2017.06.018

DO - 10.1016/j.ymthe.2017.06.018

M3 - Article

VL - 25

SP - 2289

EP - 2298

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 10

ER -

ID: 46954894