Project Description
Publications
TP01: Fate and function of scarred virus-specific T cells in chronic viral hepatitis
In HCV patients cured by antiviral therapy, HCV-specific CD8+ T cells exhibit a molecular signature of T cell exhaustion resembling a chronic scar. We hypothesize that this chronic T cell scarring reflects functional adaptation and involves not only infection-specific, but also overarching general regulatory mechanisms. We now aim to analyse intrinsic and extrinsic T cell regulators as well as the influence of clinically relevant parameters and comorbidities on virus-specific T cell scarring.Alfei F, Kanev K, Hofmann M, Wu M, Ghoneim HE, Roelli P, Utzschneider DT, von Hoesslin M, Cullen JG, Fan Y, Eisenberg V, Wohlleber D, Steiger K, Merkler D, Delorenzi M, Knolle PA, Cohen CJ, Thimme R*, Youngblood B*, Zehn D*. (2019) TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature. 571(7764):265-269. doi:10.1038/s41586-019-1326-9. *equal corresponding authors Bengsch B, Martin B, Thimme R. (2014) Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J Hepatol. 61(6):1212-1219. doi:10.1016/j.jhep.2014.07.005. Heim K, Binder B, Sagar, Wieland D, Hensel N, Llewellyn-Lacey S, Gostick E, Price DA, Emmerich F, Vingerhoet H, Kraft ARM, Cornberg M, Boettler T, Neumann-Haefelin C, Zehn D, Bengsch B, Hofmann M, Thimme R. (2020) TOX defines the degree of CD8+ T cell dysfunction in distinct phases of chronic HBV infection. Gut. 70(8):1550-1560. doi:10.1136/gutjnl-2020-322404. Hensel N, Gu Z, Sagar, Wieland D, Jechow K, Kemming J, Llewellyn-Lacey S, Gostick E, Sogukpinar O, Emmerich F, Price DA, Bengsch B, Boettler T, Neumann-Haefelin C, Eils R, Conrad C, Bartenschlager R, Grun D, Ishaque N, Thimme R*, Hofmann M*. (2021) Memory-like HCV-specific CD8(+) T cells retain a molecular scar after cure of chronic HCV infection. Nat Immunol. 22(2):229-239. doi:10.1038/s41590-020-00817-w. *equal corresponding authors Oberhardt V, Luxenburger H, Kemming J, Schulien I, Ciminski K, Giese S, Csernalabics B, Lang-Meli J, Janowska I, Staniek J, Wild K, Basho K, Marinescu MS, Fuchs J, Topfstedt F, Janda A, Sogukpinar O, Hilger H, Stete K, Emmerich F, Bengsch B, Waller CF, Rieg S, Sagar, Boettler T, Zoldan K, Kochs G, Schwemmle M, Rizzi M, Thimme R*, Neumann-Haefelin C*, Hofmann M*. (2021) Rapid and stable mobilization of CD8(+) T cells by SARS-CoV-2 mRNA vaccine. Nature. 597(7875):268-273. doi:10.1038/s41586-021-03841-4. *equal corresponding authors Schuch A, Salimi Alizei E, Heim K, Wieland D, Kiraithe MM, Kemming J, Llewellyn-Lacey S, Sogukpinar O, Ni Y, Urban S, Zimmermann P, Nassal M, Emmerich F, Price DA, Bengsch B, Luxenburger H, Neumann-Haefelin C, Hofmann M*, Thimme R*. (2019) Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. Gut. 68(5):905-915. doi:10.1136/gutjnl-2018-316641. *equal corresponding authors Seigel B, Bengsch B, Lohmann V, Bartenschlager R, Blum HE, Thimme R. (2013) Factors that determine the antiviral efficacy of HCV-specific CD8(+) T cells ex vivo. Gastroenterology. 144(2):426-436. doi:10.1053/j.gastro.2012.10.047. Thimme R, Bukh J, Spangenberg HC, Wieland S, Pemberton J, Steiger C, Govindarajan S, Purcell RH, Chisari FV. (2002) Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci U S A. 99(24):15661-15668. doi:10.1073/pnas.202608299. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. (2001) Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 194(10):1395-1406. doi:10.1084/jem.194.10.1395.Wieland D, Kemming J, Schuch A, Emmerich F, Knolle P, Neumann-Haefelin C, Held W, Zehn D, Hofmann M, Thimme R. (2017) TCF1(+) hepatitis C virus-specific CD8(+) T cells are maintained after cessation of chronic antigen stimulation. Nat Commun. 8:15050. doi:10.1038/ncomms15050.