A6 - (Dys)-regulation of the HCV-specific cellular immune response
Dr. med. Julian Constantin Schulze zur Wiesch
I. Medizinische Klinik
Several chronic virus infections are associated with a dysfunctional adaptive immune response. Primary HCV infection for instance, is characterized by the generation of functional initial immune responses in all patients, independent of disease outcome. However, in patients with chronic outcome, this immune response turns dysfunctional and cannot be detected a few weeks after primary infection. Possible underlying causes for this observed T cell dysfunction could be the overexpression of co-inhibitory molecules on HCV specific T cells, the presence of T regulatory cells and elevated levels pro-inhibitory cytokines in the liver milieu. The combination of these factors might result in the inhibition of HCV-specific T cell responses. Hence, the selective blockade of co-inhibitory molecules/Tregs could, on the one hand, lead to the partial regeneration of T cell responses against HCV. On the other hand, the effects of the chronic inflammation of the liver tissue could be counteracted which in term would lead to a decrease of inflammation-mediated liver fibrosis. However, these factors still need to be characterized further in order to understand the mechanism that lead to T cell dysfunction.
A6 in 60 SecondsVideoarchivonline seit 19.11.2012
Thus, the main aim of our study is to characterize intrahepatic and peripheral blood T cell populations at different stages of HCV infection phenotypically and functionally. The phenotypic characterization of HCV specific T cells will be carried out by using MHC I and MHC II tetramers and by analyzing the cytokine-, memory/differentiation profile of these cells. In parallel, the expression of co-inhibitory molecules and adenosine receptors on these cells shall be determined. These investigations shall contribute to the understanding of the mechanisms involved in the dysregulation of the HCV specific T cell responses in chronic HCV infection.
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
Scheurich C, Schulze Zur Wiesch J, Kim AY, Lewis-Ximenez L, Meyer T, Polywka S, Chung RT, Lauer GM
Breadth of the HCV-specific CD4+ T-cell response in spontaneous resolvers is independent of the IL-28 haplotype
J Viral Hepat. 2016 Oct;23(10):831-2. doi: 10.1111/jvh.12560. Epub 2016 Jun 27.
Eberhard JM, Kummer S, Hartjen P, Hüfner A, Diedrich T, Degen O, Lohse AW, van Lunzen J, Wiesch JS
Reduced CD161+MAIT cell frequencies in HCV and HIV/HCV co-infection. Is the liver the heart of the matter?
J Hepatol. 2016 Aug 1. pii:S0168-8278(16)30401-9. doi: 10.1016/j.jhep.2016.07.031. [Epub ahead of print]