Project Description

TP04: Characterization of follicular T helper cell responses in viral hepatitis

CD4+ T follicular helper (Tfh) cells are specialized in providing help to B cells and facilitating potent antibody responses as well as their signature cytokine IL-21 that supports CD8+ T cell responses. We propose to characterise key determinants of a successful Tfh response in acute resolving Hepatitis B virus (HBV) infection, in HBV vaccinees and by employing a mouse model of acute HBV infection. The long-term goal of this application is to design therapeutic approaches involving Tfh cells for the treatment of chronic HBV infection through induction of anti-HBs-antibodies and to support HBV-specific CD8+ T cells through Tfh cell-derived IL-21.
Raziorrouh B, Sacher K, Tawar RG, Emmerich F, Neumann-Haefelin C, Baumert TF, Thimme R, Boett- ler T. 2015. Follicular T helper cell signatures on virus-specific CD4 T cells during acute and chronic HCV-infection. Gastroenterology, accepted
Boettler T, Choi YS, Salek-Ardakani S, Cheng Y, Moeckel F, Croft M, Crotty S, von Herrath M. 2013b. 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 191:5026-35.
Boettler T, Pagni PP, Jaffe R, Cheng Y, Zerhouni P, von Herrath M. 2013a. The clinical and immunologi- cal significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes. J Autoimmun 44:40-8.
Boettler T, Moeckel F, Cheng Y, Heeg M, Salek-Ardakani S, Crotty S, Croft M, von Herrath MG. 2012b. OX40 facilitates control of a persistent virus infection. PLoS Pathog 8:e1002913.
Boettler T, Cheng Y, Ehrhardt K, von Herrath M. 2012a. TGF-β blockade does not improve control of an established persistent viral infection. Viral Immunol 25:232-8.
Thimme R, Neagu M, Boettler T, Neumann-Haefelin C, Kersting N, Geissler M, Makowiec F, Obermaier R, Hopt UT, Blum HE, Spangenberg HC. 2008. Comprehensive analysis of the alpha-fetoprotein-specific CD8+ T cell responses in patients with hepatocellular carcinoma. Hepatology 48:1821-33.
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 functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol 80:3532-40.
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 prolif- eration of virus-specific CD8+ T cells during chronic hepatitis C virus infection. J Virol 79:7860-7.