A6 (Dys)-regulation of the cellular HCV-specific immune response

A06 Schulze zur Wiesch Foto FP3

Principal Investigator:
Dr. med. Julian Constantin Schulze zur Wiesch
I. Medizinische Klinik
Universitätsklinikum Hamburg-Eppendorf
Martinistraße 52
20246 Hamburg
Tel.: +49-40-7410-20977
E-Mail: jschulze@uke.uni-hamburg.de

Participating staff:

Christin Ackermann M.Sc. – Doktorandin
Silke Kummer– MTA
Verena Matzat – BTA

Project description

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.

A06 in 60 SecondsVideoarchiv

A06 in 60 Seconds online seit 17.12.2018

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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.