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Klinik für Innere Medizin IIGastroenterologie, Hepatologie, Endokrinologie und Infektiologie

AG BÖTTLER
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Research interest

Our research focuses on translational human T cell immunology, with a particular emphasis on antigen-specific T cell responses in infection and cancer, using high-dimensional and multimodal immune profiling approaches. We study how T cell immunity is regulated in acute resolving versus chronic disease settings and how these distinct contexts shape protective or dysfunctional immune responses in patients. A central theme of our work is the role of the inhibitory receptor PD-1 in controlling T cell activation, maintaining immune homeostasis, and preventing immunopathology. We investigate how this pathway contributes to immune balance, how it is altered across different disease states, and how therapeutic interventions reshape T cell differentiation, function, and fate in humans. A growing focus of our lab is the analysis of human tissue-derived T cell populations to understand how local microenvironments shape T cell function and drive disease progression. In a translational context, we aim to identify immune mechanisms and signatures that predict disease course, clinical outcome, and response to therapy.

Group of Tobias Böttler

Prof. Dr. Tobias Böttler (Group leader)   
Dr. Rafael Käser (Clinician Scientist)+49 (0) 761/270-35500
Carolin Heni (MD student)+49 (0) 761/270-35110
Lara Kelsch (PhD student)+49 (0) 761/270-33961
Dr. Giuseppe Rusignuolo (Clinician Scientist)+49 (0) 761/270-32625
Jill Werner (PhD student)+49 (0) 761/270-35110
Layla Höher (MD student)+49 (0) 761/270-35110
Katharina Baumeister (PostDoc) 

Funding

Sonderforschungsbereich-TRR179 (Deutsche Forschungsgemeinschaft, DFG)

Exzellenz-Stipendium 2021 (Else-Kröner-Fresenius-Stiftung, EKFS)

TTU Hepatitis (Deutsches Zentrum für Infektionsforschung, DZIF)

  1. Reinscheid M, Weißer J, Maier NP, Reeg D, Hafkemeyer PL, Kelsch L, Rusignuolo R, Arnold J, Emmerich F, Walker A, Froehlich Y, Cherukunnath A, Timm J, Picelli S, Bengsch B, Sagar, Thimme R*, Hofmann M*, Boettler T.* 2026 *equal contribution
    Distinct T helper cell trajectories sustain long-term virus-specific CD4+ T cell immunity in acute versus chronic infection in humans. Immunity. Accepted
  2. Zhang Z, Langenbach M, Sagar S, Fetsch V, Stritzker J, Severa E, Meng K, Winkler F, Rana N, Zoldan K, Godbole I, Solis S, Weber JS, Rafei-Shamsabadi D, Lehr S, Diehl R, Venhoff AC, Voll RE, Buettner N, Neumann-Haefelin C, Boettler T, Hofmann M, Boerries M, Meiss F, Zeiser R, Thimme R, Herati RS, Bengsch B. 2025
    Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1+CD8+ T cells. Nat Immunol. 26(1):92-104.
  3. Heim K, Sagar, Sogukpinar Ö, Llewellyn-Lacey S, Price DA, Emmerich F, Kraft ARM, Cornberg M, Kielbassa S, Knolle P, Wohlleber D, Bengsch B, Boettler T, Neumann-Haefelin C, Thimme R, Hofmann M. 2024
    Attenuated effector T cells are linked to control of chronic HBV infection. Nat Immunol. 25(9):1650-1662.
  4. Csernalabics B, Marinescu MS, Maurer L, Kelsch L, Werner J, Baumann K, Zoldan K, Panning M, Reuken P, Bruns T, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Dao Thi VL, Boettler T. 2024
    Efficient formation and maintenance of humoral and CD4 T-cell immunity targeting the viral capsid in acute-resolving hepatitis E infection. J Hepatol. 80(4):564-575.
  5. Globig AM, Mayer LS, Heeg M, Andrieux G, Ku M, Otto-Mora P, Hipp AV, Zoldan K, Pattekar A, Rana N, Schell C, Boerries M, Hofmann M, Neumann-Haefelin C, Kuellmer A, Schmidt A, Boettler T, Tomov V, Thimme R, Hasselblatt P, Bengsch B. 2022
    Exhaustion of CD39-Expressing CD8+ T Cells in Crohn's Disease Is Linked to Clinical Outcome. Gastroenterology. 163(4):965-981.e31.
  6. Boettler T, Csernalabics B, Salié H, Luxenburger H, Wischer L, Salimi Alizei E, Zoldan K, Krimmel L, Bronsert P, Schwabenland M, Prinz M, Mogler C, Neumann-Haefelin C, Thimme R, Hofmann M, Bengsch B. 2022 
    SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. J Hepatol. 2022 Sep;77(3):653-659.
  7. Wild K, Smits M, Killmer S, Strohmeier S, Neumann-Haefelin C, Bengsch B, Krammer F, Schwemmle M, Hofmann M, Thimme R, Zoldan K, Boettler T. 2021
    Pre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination. Nat Commun. 8;12(1):6720.
  8. Zoldan K, Ehrlich S, Killmer S, Wild K, Smits M, Russ M, Globig AM, Hofmann M, Thimme R, Boettler T. 2021
    Th1-Biased Hepatitis C Virus-Specific Follicular T Helper-Like Cells Effectively Support B Cells After Antiviral Therapy. Front Immunol. 30;12:742061.
  9. Basho K, Zoldan K, Schultheiss M, Bettinger D, Globig AM, Bengsch B, Neumann-Haefelin C, Klocperk A, Warnatz K, Hofmann M, Thimme R, Boettler T. 2021
    IL-2 contributes to cirrhosis-associated immune dysfunction by impairing follicular T helper cells in advanced cirrhosis. J Hepatol. 74(3):649-660.
  10. Schulien I, Kemming J, Oberhardt V, Wild K, Seidel LM, Killmer S, Sagar, Daul F, Salvat Lago M, Decker A, Luxenburger H, Binder B, Bettinger D, Sogukpinar O, Rieg S, Panning M, Huzly D, Schwemmle M, Kochs G, Waller CF, Nieters A, Duerschmied D, Emmerich F, Mei HE, Schulz AR, Llewellyn-Lacey S, Price DA, Boettler T*, Bengsch B*, Thimme R*, Hofmann M*, Neumann-Haefelin C*. 2021 *equal contribution
    Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells. Nat Med. 27(1):78-85.
  11. Smits M, Zoldan K, Ishaque N, Gu Z, Jechow K, Wieland D, Conrad C, Eils R, Fauvelle C, Baumert TF, Emmerich F, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Boettler T. 2020
    Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination. J Clin Invest. 130(2):998-1009.
  12. Jacobi FJ, Wild K, Smits M, Zoldan K, Csernalabics B, Flecken T, Lang J, Ehrenmann P, Emmerich F, Hofmann M, Thimme R, Neumann-Haefelin C, Boettler T. 2019
    OX40 stimulation and PD-L1 blockade synergistically augment HBV-specific CD4 T cells in patients with HBeAg-negative infection. J Hepatol. 70(6):1103-1113.
  13. Adam L, Zoldan K, Hofmann M, Schultheiss M, Bettinger D, Neumann-Haefelin C, Thimme R, Boettler T. 2018
    Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. Hepatol Commun. 7;2(9):1051-1063.
  14. Raziorrouh B, Sacher K, Tawar RG, Emmerich F, Neumann-Haefelin C, Baumert TF, Thimme R, Boettler T. 2016
    Virus-Specific CD4+ T Cells Have Functional and Phenotypic Characteristics of Follicular T-Helper Cells in Patients With Acute and Chronic HCV Infections. Gastroenterology. 150(3):696-706.e3.
  15. Boettler T, Schneider D, Cheng Y, Kadoya K, Brandon EP, Martinson L, Herrath MV. 2016
    Pancreatic tissue transplanted in TheraCyte™ encapsulation devices are protected and prevent hyperglycemia in a mouse model of immune-mediated diabetes. Cell Transplant. 25(3):609-14.
  16. Boettler T, Choi YS, Salek-Ardakani S, Cheng Y, Moeckel F, Croft M, Crotty S, von Herrath M. 2013
    Exogenous OX40 stimulation during lymphocytic choriomeningitis virus infection impairs follicular Th cell differentiation and diverts CD4 T cells into the effector lineage by upregulating Blimp-1. J Immunol. 15;191(10):5026-35.
  17. Boettler T, Pagni PP, Jaffe R, Cheng Y, Zerhouni P, von Herrath M. 2013
    The clinical and immunological significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes. J Autoimmun. 44:40-8.
  18. Boettler T, Moeckel F, Cheng Y, Heeg M, Salek-Ardakani S, Crotty S, Croft M, von Herrath MG. 2012
    OX40 facilitates control of a persistent virus infection. PLoS Pathog. 8(9):e1002913.
  19. Boettler T, Cheng Y, Ehrhardt K, von Herrath M. 2012
    TGF-β blockade does not improve control of an established persistent viral infection. Viral Immunol. 25(3):232-8.
  20. Boettler T, Panther E, Bengsch B, Nazarova N, Spangenberg HC, Blum HE, Thimme R. 2006
    Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol. 80(7):3532-40.
  21. Boettler T, Spangenberg HC, Neumann-Haefelin C, Panther E, Urbani S, Ferrari C, Blum HE, von Weizsäcker F, Thimme R. 2005
    T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J Virol. 79(12):7860-7.

  1. Weisser J, Boettler T. 2025
    CD4 T cells and B cell help - when exhausted cells can still function. JHEP Rep. 7(7):101435.
  2. Wittkop L, Boettler T. 2023
    More than shots in the dark: driving vaccine efficacy in cirrhosis. Gut. 73(1):8-9.
  3. Boettler T, Gill US, Allweiss L, Pollicino T, Tavis JE, Zoulim F. 2022
    Assessing immunological and virological responses in the liver: Implications for the cure of chronic hepatitis B virus infection. JHEP Rep.4(6):100480.
  4. Boettler T, Lohmann V, Bartenschlager R. 2019
    [Hepatitis C: From Individual Cure to Worldwide Elimination?]. Dtsch Med Wochenschr. 144(8):535-542.
  5. Luxenburger H, Neumann-Haefelin C, Thimme R, Boettler T. 2018
    HCV-Specific T Cell Responses During and After Chronic HCV Infection. Viruses. 17;10(11).
  6. Boettler T, Thimme R. 2018
    Lost in Inflammation: The Functional Conversion of Regulatory T Cells in Acute Hepatitis A Virus Infection. Gastroenterology. 154(4):798-800.
  7. Boettler T, Thimme R, Neumann-Haefelin C. 2015
    [Cure of chronic Hepatitis B and C: vision versus reality]. Dtsch Med Wochenschr. 140(14):1056-62.
  8. Boettler T, Moradpour D, Thimme R, Zoulim F. 2014
    Bridging basic science and clinical research: the EASL Monothematic Conference on Translational Research in Viral Hepatitis. J Hepatol. 61(3):696-705.
  9. Boettler T, von Herrath M. 2012
    IL-7 receptor α blockade, an off-switch for autoreactive T cells. Proc Natl Acad Sci U S A. 31;109(31):12270-1.
  10. Boettler T, Cunha-Neto E, Kalil J, von Herrath M. 2012
    Can an immune-regulatory vaccine prevent HIV infection? Expert Rev Anti Infect Ther. 10(3):299-305.
  11. Boettler T, von Herrath M. 2011
    Protection against or triggering of Type 1 diabetes? Different roles for viral infections. Expert Rev Clin Immunol. 7(1):45-53.