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.

A6 in 60 SecondsVideoarchiv

online 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.

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