Project Description

TP04: Regulation of virus-specific CD4 T helper cell responses in viral hepatitis

CD4 T helper cells are central players in the regulation of the antiviral immune response. They are particularly important for the maintenance of cytotoxic CD8 T cell responses and the emergence of antibody-producing B cells. Distinct subpopulations of the CD4 T helper compartment are involved in these functions. This project aims to define the composition of the CD4 T helper compartment in the setting of acute and chronic viral hepatitis. These observations could provide a blueprint of successful CD4 T cell responses that could inform vaccine design.
A. Smits M, Zoldan K, Wieland D, Ishaque N, Gu Z, Jechow K, Conrad C, Eils R, Fauvelle C, Baumert TF, Emmerich F, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Boettler T. 2019. Follicular T helper cells shape HCV-specific CD4 T cell repertoire after viral elimination. J Clin Invest. 2019 Nov 7. pii: 129642. doi: 10.1172/JCI129642. [Epub ahead of print]
B. Ackermann C, Smits M, Woost R, Eberhard JM, Peine S, Kummer S, Marget M, Kuntzen T, Kwok WW, Lohse AW, Jacobs T, Boettler T, Schulze Zur Wiesch J. 2019. HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory mole-cules. Sci Rep. 9(1):10624.
C. 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.
D. Schuch A, Zecher BF, Müller PA, Correia MP, Daul F, Rennert C, Tauber C, Schlitt K, Boettler T, Neumann-Haefelin C, Hengel H, Pircher H, Cerwenka A, Thimme R, Hofmann M. 2019. NK-cell responses are biased towards CD16-mediated effector functions in chronic hepatitis B virus infection. J Hepatol. 70(3):351-360.
E. Luxenburger H, Graß F, Baermann J, Boettler T, Marget M, Emmerich F, Panning M, Thimme R, Nitsch-ke K, Neumann-Haefelin C. 2018. Differential virus-specific CD8(+)T-cell epitope repertoire in hepatitis C virus genotype 1 versus 4. J Viral Hepat. 25(7):779-790.
F. 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
G. 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. 191(19):5026-35.
H. 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:e1002913.
I. Boettler T, Panther E, Bengsch B, Nazarova N, Spangenberg HC, Blum HE, Thimme R. 2006. Expres-sion of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies function-ally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol. 80(7):3532-40.
J. 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 pro-liferation of virus-specific CD8+ T cells during chronic HCV infection. J Virol. 79(12):7860-7.