Project Description
Public­ations

TP01: Fate and function of memory-like virus-specific CD8+ T cells in chronic viral hepatitis

TP01 is based on the hypothesis that duration of antigen recognition might be a central determinant of the transcriptional profile of virus-specific CD8+ T cells. Hence, a transcriptional profile characteristic for persisting antigen recognition is inherent to memory-like virus-specific CD8+ T cells that emerge during chronic viral hepatitis and that are maintained after viral clearance. With the proposed work program we aim to define the fate, the biological role and the translational value of memory-like virus-specific CD8+ T cells in chronic viral hepatitis. We will therefore assess molecular determinants, driving immunological factors and the memory potential of memory-like virus-specific CD8+ T cells.
A. Alfei F, Kanev K, Hofmann M, Wu M, Ghoneim HE, Roelli P, Utzschneider DT, Hösslin M, Cullen J, Fan Y, Eisenberg V, Wohlleber D, Steiger K, Merkler D, Delorenzi M, Knolle PA, Cohen C, Thimme R*, Youngblood B*, Zehn D*. 2019. Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection. Nature. 2019 571(7764):265-269* co-corresponding au-thors
B. Karimzadeh H*, Kiraithe MM*, Oberhardt V*, Salimi Alizei E, Bockmann J, Schulze Zur Wiesch J, Budeus B, Hoffmann D, Wedemeyer H, Cornberg M, Krawczyk A, Rashidi-Alavijeh J, Rodríguez-Frías F, Casillas R, Buti M, Smedile A, Alavian SM, Heinold A, Emmerich F, Panning M, Gostick E, Price DA, Timm J, Hofmann M, Raziorrouh B, Thimme R, Protzer U, Roggendorf M, Neumann-Haefelin C. 2019. Mutations in Hepatitis D Virus Allow It to Escape Detection by CD8+ T Cells and Evolve at the Population Level. Gastroenterology. 156(6):1820-1833 *equal contribution
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. pii: S0168-8278(19)30131-X. doi: 10.1016/j.jhep.2019.02.016.
D. Schuch A, Salimi Alizei E*, Heim K*, Wieland D, Kiraithe MM, Kemming J, Llewellyn-Lacey S, Soguk-pinar Ö, Ni Y, Urban S, Zimmermann P, Nassal M, Emmerich F, Price DA, Bengsch B, Luxenburger H, Neumann-Haefelin C, Hofmann M*, Thimme R*. 2019a. Phenotypic and functional differences of HBVcore- versus HBVpolymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. GUT. 68(5) *equal contribution
E. Schuch A, Zecher BF, Müller PA, Correia MP, Daul F, Rennert C, Tauber C, Schlitt K, Böttler T, Neumann-Haefelin C, Hengel H, Pircher H, Cerwenka A, Thimme R, Hofmann M. 2019b. NK-cell re-sponses are based towards CD16-mediated effector functions in chronic hepatitis B virus infection. J Hepatol. 70(3):351-360
F. Manske K, Kallin N, König V, Schneider A, Kurz S, Bosch M, Welz M, Cheng RL, Bengsch B, Steiger K, Protzer U, Thimme R, Knolle PA, Wohlleber D. 2018. Outcome of Antiviral Immunity in the Liver Is Shaped by the Level of Antigen Expressed in Infected Hepatocytes. Hepatology. 68(6):2089-2105
G. Grünvogel O, Colasanti O, Lee JY, Klöss V, Belouzard S, Reustle A, Esser-Nobis K, Hesebeck-Brinckmann J, Mutz P, Hoffmann K, Mehrabi A, Koschny R, Vondran FWR, Gotthardt D, Schnitzler P, Neumann-Haefelin C, Thimme R, Binder M, Bartenschlager R, Dubuisson J, Dalpke AH, Lohmann V. 2018. Secretion of Hepatitis C Virus Repilcation Intermediates Reduces Activation of Toll-Like Recep-tor 3 in Hepatocytes. Gastroenterology. 154(8):2231-2251.
H. Utzschneider DT, Delpoux A, Wieland D, Huang X, Lai CY, Hofmann M, Thimme R, Hedrick SM. 2018. Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continu-ous Expression of FOXO1. Cell Rep. 22(13):3454-3467
I. 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 *equal contribution
J. Utzschneider DT, Charmoy M, Chennupati V, Pousse L, Ferreira DP, Calderon-Copete S, Danilo M, Alfei F, Hofmann M, Wieland D, Pradervand S, Thimme R, Zehn D, Held W. 2016. T Cell Factor 1-Expressing Memory-like CD8(+) T Cells Sustain the Immune Response to Chronic Viral Infections. Immunity. 45(2):415-2