A6 (Dys)-regulation of the cellular HCV-specific immune response
Dr. med. Julian Constantin Schulze zur Wiesch
I. Medizinische Klinik
Christin Ackermann M.Sc. – Doktorandin
Silke Kummer– MTA
Verena Matzat – BTA
Functional impairment of the adaptive virus-specific immune response are characteristic features of many viral infections. In hepatitis C virus (HCV) infection, it is currently unclear why virtually all patients initially generate a virus-specific CD4 + T cell response, but this is dysfunctional in most cases and can no longer be detected after the first weeks of HCV infection. The CD4 + T cell response plays a central role in the coordination of the B-cell as well as the CD8 + T cell response. In acute, untreated HCV infection, CD4 + T cells lose their functionality under the influence of co-inhibitory molecules, and HCV infection takes a chronic course in the majority of patients. The detailed elucidation of the surface expression patterns of various inhibitory and stimulatory molecules on HCV-specific CD4 + T cells can help to better understand this loss of function.
A6 in 60 SecondsVideoarchivonline seit 19.11.2012
The focus of our investigations is the ex vivo characterization of the expression pattern of co-inhibitory and stimulatory molecules on HCV-specific MHC class II tetramer positive CD4 + T cells at different stages of HCV infection.
Our work from the previous funding periods shows that HCV-specific CD4 + cells of patients with acute or chronic HCV infection have a higher co-expression of inhibitory receptors compared to patients with spontaneously healed HCV infection. In particular we were able to observe the PD-1 / TIGIT co-expression.
Further functional in vitro experiments must show to what extent a possible co-blockade of these two molecules can lead to a restoration of the functional properties of HCV-specific CD4 + T cells.
Landahl J, Bockmann JH, Scheurich C, Ackermann C, Matzat V, Heide J, Nuurei T, D’Antonio G, von Felden J, Sette A, Peine S, Lohse AW, Luetgehetmann M, Marget M, Sidney J, Schulze Zur Wiesch J.
Detection of a broad range of low level MHC class II-restricted Hepatitis Delta Virus (HDV)-specific T cell responses regardless of the clinical status.
J Infect Dis. 2018 Sep 23. doi: 10.1093/infdis/jiy549. [Epub ahead of print]
Beudeker BJB, van Oord GW, Arends JE, Schulze Zur Wiesch J, van der Heide MS, de Knegt RJ, Verbon A, Boonstra A, Claassen MAA.
MAIT-cell frequency and function in blood and liver of HCV mono- and HCV/HIV co-infected patients with advanced fibrosis
Liver Int. 2017 Aug 9. doi: 10.1111/liv.13544. [Epub ahead of print]
Wehmeyer MH, Ingiliz P, Christensen S, Hueppe D, Lutz T, Simon KG, Schewe K, Boesecke C, Baumgarten A, Busch H, Rockstroh J, Schmutz G, Kimhofer T, Berger F, Mauss S, Wiesch JSZ
Real-world effectiveness of sofosbuvir-based treatment regimens for chronic hepatitis C genotype 3 infection: results from the multicenter German hepatitis C cohort (GECCO-03)
J Med Virol. 2017 Jul 15. doi: 10.1002/jmv.24903. [Epub ahead of print]
Deterding K, Spinner CD, Schott E, Welzel TM, Gerken G, Klinker H, Spengler U, Wiegand J, Schulze Zur Wiesch J, Pathil A, Cornberg M, Umgelter A, Zöllner C, Zeuzem S, Papkalla A, Weber K, Hardtke S, von der Leyen H, Koch A, von Witzendorff D, Manns MP, Wedemeyer H; HepNet Acute HCV IV Study Group
Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study.
Lancet Infect Dis. 2017 Feb;17(2):215-222. doi: 10.1016/S1473-3099(16)30408-X. Epub 2016 Oct 28